Madrid, capital of Spain and home of the royal family. The city center with great architecture is amazingly small, with nice places to enjoy local food and wines and very walkable.
Barcelona is capital of Catalonia and world-famous for soccer and architecture. You must visit the cathedral Sagrada Familia, designed by Gaudi, that has been under construction since 1883. Camp Nou, where FC Barcelona resides, is an experience of a different kind.
Seville is the capital of the Andalusian region that also includes Malaga and Granada. It is very Spanish here with historical buildings, Flamenco Music & Dance, horses, Paella and Sangria. Note that it can be really hot (40°C and more) in Summer...
Cadiz is one of the oldest cities in Europe. It's location is quite unique, since it is surrounded almost completely by water (similar to Venice). James Bond used the city to resemble Cuba.
San Sebastian is a superb beach location just west of the Pyrenees with excellent food (tapas). It should be on everyone's itinerary.
Santiago de Compostela is the capital of Galicia and the end point of the pilgrimage "Camini de Santiago" and the apostel James should be buried here. The journey here is different from other journeys since people like to either walk or bike.
Valencia is an import coastal city with unique architecture, including a beautiful market hall. It is also home to the Paella de Valencia, the original!
Jerez is known mainly for two things: 1) the bodegas for the finest Sherries and 2) the Equestrian School for ultimate horse back riding demonstrations. Add to this great weather, some flamenco and lots of orange trees and then you know something about Jerez de la Frontera.