Oh, wow, what a question. I have a million ideas!
How about a week on the northern coast enjoying beautiful old towns/fishing villages and great fish? Luarca, Cudillero, Llanes, Lastres would be my favorites. The FEVE train runs all along the coast making transportation pretty easy, and then at the end just hop on the bus/train and get to Madrid and the flight homoe.
Or head down towards Madrid and visit the classic trio of Segovia (with the BEAUTIFUL palace at LaGranja about 10 kms away), Avila and Salamanca, ending up with a few days in Madrid. These are all amazing places.
Or zoom south on a fast train or two and spend the time in Andalucia -- something totally different from what you will have seen -- Granada, Cordoba and Sevilla probably can't all be "properly" visited in a week but if you had a few extra days as you might, that's an option.
Or Barcelona with a few day trips -- up the coast to places like San Pere de Rodas, down to Valencia, into the province of Girona.
Or for something totally different, spend a week in Portugal. Lisbon is a great city, less prettified than either Madrid or Barcelona, but has a lot of history and a lot of charm. It's cheaper than Spain, great absolutely great fresh fish, lots of good little day trips from Lisbon too.
You have an absolutely impossible decision to make! The only thing I wouldn't do is to squeeze both Barcelona and Madrid into this trip. Lots of distance, two big cities. Both of them have so much to offer and so much in the vicinity that you would have a full week in either place.
Buen camino, Laurie
p.s. and just to be different, I want to say that I personally prefer Madrid to Barcelona any day. Barcelona is in a better location, is younger and hipper and more touristy, but Madrid just throbs with life and is a stunning monumental city. Not saying I don't like Barcelona, of course.