Here you'll find the sight that sets each of Spain's cities apart from all the others. Most cities have many, many more sights than these few, but with this list, you'll never be in any doubt about what makes a particular city so famous.
Madrid: The Golden Triangle of Art Museums
The Museo del Prado, the Reina Sofia, and the Thyssen-Bornemisza are three of the best art museums in Europe, just a few steps apart in a small triangle close to Atocha train station.
The Prado is Madrid's Louvre, with a phenomenal number of classical Spanish paintings and sculptures. The Reina Sofia is Spain's premier modern art museum, with Picasso's Guernica as the biggest draw. The Thyssen-Bornemisza has one of the best private art collections in the world.
If you have even a passing interest in art, these museums are a must for any visitor to Madrid. And as they are close to both the Atocha train station and the airport bus so you could visit one in a short stopover or when changing trains.
Madrid's fantastic day trips include Segovia, Toledo, Avila, the Valle de los Caidos are all musts.
Madrid has the most international flights and the best transport network in the country, making it the ideal place to start your vacation. Everything is easy to reach from Madrid. Apart from the aforementioned day trips, there's also the high-speed AVE train to Cordoba, Seville, Barcelona, Cuenca, and Valencia.
Barcelona: La Sagrada Familia
Love or loathe it, you have to see Gaudi's famous unfinished basilica in Barcelona to judge for yourself. It's one of the most extravagant buildings ever created and divides opinion like few other structures on earth.
Be sure to walk all the way around the Sagrada Familia - one facade shows the Passion of Christ, the other shows the nativity scene. The architectural style on each facade is quite different.
Figueres and Madrid are both on the high-speed AVE train from here. There are also good train connections to Valencia.
Seville: Barrio Santa Cruz
Seville is split up into several famous barrios (neighborhoods) but the most famous is Barrio Santa Cruz. The architecture is the most classically 'Spanish', the restaurants are fantastic, and there is a good chance you'll come across some flamenco too.
The cathedral, with its Arabic Giralda tower, the fantastic tapas bars, bullfighting, and flamenco. Seville is where you'll find everything you expect to see in Spain.
Granada, Cadiz, and Jerez. There's also the high-speed AVE train to Madrid, via Cordoba.
Malaga: The Vibe
Despite stereotypes, Spain is not the all-year-round beach paradise that many think it is. Northern Spain can get very wet for half the year and Barcelona has several cold months.
The south coast of Spain, on the other hand, is a lot closer to the idyllic image of year-round sunshine and warm weather. If you want a good chance of some nice weather in February or March, your best bet is to visit somewhere along the Costa del Sol. And if you're looking for a city with good nightlife, a variety of restaurants, and a little culture, Malaga is your best bet.
No, we didn't pick a specific 'sight' for Malaga. It's not that kind of city. Don't expect a Madrid, a Barcelona, or a Seville from Malaga. There are many, many better cities to visit in Spain for cultural attractions and the fact that so many tourists never get further than Malaga cab be frustrating. But if warm weather and a beach are all you're looking for, then Malaga is your best bet.
There's a Thyssen-Bornemisza museum but it's not as good as the one in Madrid. There's a Picasso museum, but it's not as good as the one in Barcelona. Fried fish tapas bars are good, without the pretensions of Seville's or Barcelona's and at a much better price, but they're better along the coast in Cadiz.
Granada is the nearest. There's also the high-speed AVE train to Cordoba and Madrid.
Granada: Alhambra and Free Tapas
After a morning at the Alhambra, don't forget to go for tapas. In Granada, the tapas is free! Buy a beer or glass of wine and get a small portion of paella or fried fish or whatever they're serving at the time. The best street for this is Calle Elvira, though this has got quite touristy, with bars doing their best to out-tapa each other in quantity if not quality. Explore off the beaten path for even more delights...
The Albaicin Moorish quarter, the Sacromonte gypsy quarter, the Sierra Nevada and Alpujarras mountains, and the 'Moroccan teahouses'.
Seville, Cordoba, and Granada.
Cordoba: The Mezquita
Cordoba's Mezquita was once the biggest mosque in Europe. Today it is the city's cathedral, but it hasn't had a complete makeover so most of its original Arabic charm is still present.
Check out the white-washed walls of the old town, reminiscent of a small pueblo blanco and hardly what you'd expect of a city. Be sure to look inside the courtyards of the houses where possible - during the month of May, there is a competition for the best decorated patio.
Cordoba is on the high-speed AVE train line from Madrid to Seville. Granada and Malaga aren't too far either.
San Sebastian: Gourmet Tapas
San Sebastian turned tapas (or pintxos in the local Basque language) into high-art. Elements of molecular gastronomy find their way into classic Spanish and Basque dishes, all served in convenient small portions that encourage bar hopping and adventurously trying dishes you perhaps ordinarily wouldn't. Wash it down with the local wine, Txakoli, which is a tart white wine, or with Rioja.
San Sebastian has the best city beach in all of Spain.
Bilbao is an hour away by bus. If flying from the United States, Madrid is closer than Barcelona, despite the San Sebastian and Barcelona are both in the north of the country.
Bilbao: Guggenheim Museum
You don't even need to go inside to appreciate Bilbao's Guggenheim: Its Frank Gehry-designed exterior looks like a cruise liner made by NASA has crash-landed in the city. But you should go inside because the Guggenheim is one of Spain's two best modern art museums (along with the Reina Sofia in Madrid). Plus, it has a great restaurant (reserve a table for their excellent lunch menu).
Bilbao's Siete Calles (Seven Streets) old town area.
San Sebastian is an hour away by bus.
Paella was invented in the rice fields of Valencia. Despite its international fame as a seafood dish, the original paella had meat instead of the typical mussels and calamari. There are lots of good paella restaurants in Valencia, but the best place to go is out to the Albufera area just outside town.
The Las Fallas festival in March and the City of Arts and Sciences.
Cuenca is on the high-speed AVE train line to Madrid. There are also good transport connections to Barcelona.
Toledo: The Full Experience
It's not easy to pick Toledo's 'must-see' sight. It has fantastic city walls (though Avila's are better), a fascinating heritage of Christian, Jewish, and Muslim faiths, some great museums, and beautiful views of the area around the city. But ultimately, the best thing about Toledo is all of it. Wandering around the streets, popping into a museum if it takes your fancy, stopping in a bar for a beer, or merely admiring the architecture. The entire city gets our vote.
The nearby wine regions are worth a visit too. There's even a guided tour that will take you to both Toledo and the wine region on the same day.
Madrid is just half an hour away by train.
Segovia: The Roman Aqueduct
Segovia's Roman aqueduct is an impressive feat of engineering. It has stood for almost two thousand years and, even more remarkably, no mortar was used in its construction - the rocks are merely stacked together with only their weight keeping the structure together.
The Alcazar. Some say it inspired Cinderella's castle in the Disney movie (more say the similar-looking German castles are a more likely inspiration).
Segovia is close to Madrid and is often combined on a day trips from Madrid.
Ronda: Historic Bridges Over the Tajo Ravine
Ronda was one of the final Muslim strongholds during the Reconquista, thanks to its defensive position straddling a steep ravine. The bridges that run between the two parts of the city over the Tajo ravine are Ronda's most famous sights.
The bullring was where bullfighting was invented!
Granada and Seville are both quite close.
Salamanca: Plaza Mayor
Salamanca's main square, Plaza Mayor, is easily its most famous sight. Built out of locally-quarried yellow sandstone (in fact, most of the old town is), the walls are adorned with portraits of rulers from Spain's history. Look out for the picture of Franco - it's usually got paint thrown on it in protest!
The cathedral (also made out of sandstone) has some intricate carvings on it. Look out for the ice cream and the astronaut, cheekily added during a recent restoration.
Salamanca is close to Madrid, but at more than two hours each way, it's best to visit overnight.
Santiago de Compostela: 12th Century Cathedral
Santiago's old town is a cobblestoned marvel (it's a UNESCO World Heritage Site).
Sherry was invented in Jerez (it takes its name from the Arabic name for the city, Xeres) and all sherry is made either here in Jerez, Sanlúcar de Barrameda or El Puerto de Santa María.
What sets Jerez apart from most wine cities is that the bodegas are in the center of town, so there's no need to organize transport and designated drivers.
Cadiz, Seville, and Gibraltar are all nearby.
Cadiz: Fried Fish
The fish from the UK's ubiquitous 'fish and chips' was a Spanish invention, in particular from the Andalusian coast and Cadiz itself. The freiduria Las Flores in Cadiz is the best place to get fried fish, with more than a dozen varieties on offer.
If you can't make it to Cadiz, another great place to get fried fish is at the Freiduria Puerta de la Carne in Seville.
The old town's unique location on the end of a narrow peninsula gives it a wonderful microclimate all of its own.
Jerez and Seville are both nearby (you can even visit both).
Leon: Tapas Bars of Barrio Húmedo
Leon is second only to Granada for serving tapas the way it was meant to be served: as a free accompaniment to your drink. The Barrio Húmedo ('damp quarter') is Leon's attractive old town area, the perfect backdrop for your bar-hopping tapas trail!
None of the cities are especially close, but Oviedo would you be your nearest option.
Burgos: The Cathedral
The 13-century Burgos cathedral is the only cathedral in Spain that is a UNESCO World Heritage Site entirely in its own right (several old towns make the list, partly because of their cathedral, and Seville cathedral makes the list as a joint entry with the Alcazar and Archivo de Indias). It's an imposing sight, far bigger than would seem appropriate for a city of this size.
Burgos is just over an hour's drive from Logroño and between 90 minutes' and two hours' drive from both Bilbao and Leon.