well what are you into? Big city with nightlife and mad soccer (like the campe nou and santiago Bernabeu in Barcelona and Madrid) or getting away from it all in the country?
Personally I like Barcelona better than Madrid as a city, because it's older and more beautiful, has the Ramblas and all the amazing cathedrals and other buildings. But Madrid has more greenery, and it has the Prado and El Escorial, if you're into art. Both cities have an amazing nightlife. I can't say I know much about the south -- I've never been there.
If you're looking for a more rustic experience, go to the mae strat. DO IT. It was amazing, and each town has its own running of the bulls in august. Each town. It's a mountain region, and the views are amazing. So are the sunsets, if you go for that. Lots mof relaxation time, and a great area to just chill and read.
If you want to know more about a specific area, ask me, or even better, one of the spanish members who might live in one of the places where I've never been.