We did similar, the month of April beginning in Barcelona and ending in Madrid. I did a trip report called Spain: Clean toilets, affordable lodging (sorry the title isn't very appealing) here. You may find it useful.
We started in Barcelona on the last day of March. Easter was the first week of April in 2012 and we spent most of Semana Santa (Holy Week) in Barcelona. This was a mistake. Barcelona does less for Semana Santa than anywhere in Spain (read George Orwell's "Homage to Catalonia" if you're interested in a good historical context), so I'd try to plan Holy Week elsewhere.
We picked up a car in Barcelona (a short walk from our hostal off the Ramblas). We bring only one carry-on each, so a compact, diesel with standard transmission is my first choice. The gas mileage is beyond amazing (better than 50 miles to a gallon). We drove first to Montserrat. It was nice to see but rained so we didn't do any hiking.
From there we drove to Zaragosa. We were there Holy Thursday and the processions were amazing, hundreds of drums along with the normal procession floats. This was one of the best travel experiences of my life, very local, very friendly, very affordable lodging. My biggest problem was getting to our hotel with so many street closures for the processions (which went all day and all night).
We drove north to Pamplona, a decent look around but a really subdued Good Friday procession compared to what we'd seen the night before. On the way to Pamplona, however, we stopped to see a castle in Olite (maybe 30 minutes driving distance before Pamplona). This is a great castle visit. I highly recommend it. It's not a ruin but isn't furnished - which means you get free reign of the place. A good handheld guide gives you an idea of what the castle would have been like when the Kings of Navarre lived there.
From Pamplona we visited San Sebastian (Donostia to the locals). I like the place but it's definitely best experienced during the high summer months. It was mostly cold and rainy in April - we could have skipped it and come back during a summer trip through the Basque region.
After Donostia, we drove through the Rioja region - staying in Burgos, Valladolid, and Salamanca. Around Valldolid are some of the best castles La Mota, Coca and Penafiel. We visited all three.
From Salamanca, we visited Avila, Segovia, and Toledo (we bypassed Madrid until the end of our trip).
After Toledo we headed south. We drove through Consuegra, then to Belmonte Castle, and down to Valdepenas. I'd skip Consuegra, stop in Aranjuez instead then down to Belmonte and Valdepenas. Consuegra is neat because it has a small castle as well as old windmills. The area's hills are dotted with the old windmills, however, so you don't need to visit Consuegra to see them and Belmonte is by far a better castle visit.
We totally missed Cuenca. It just wasn't convenient to our itinerary. I wish I could have included it.
We stopped in Jaen before going to Granada. We could have skipped it. We went because it's supposed to have great Arab baths - which were closed for rennovations.
Granada was great. We travel without reservations - only a rough idea of where and when we'll be - which made Granada a little tough. I ended up with my fourth choice of lodging (from a list prepared ahead of our trip) - this is the only time we had something other than our first choice. It was also awkward seeing the Alhambra. Without reservations or Rick's advice about how to see Alhambra without advance reservations, we might not have seen it (Rick's book was worth the money for this advice alone). A Sambra performance in a cave-home was another highlight.
From Granada, we made a short stop in Antequera to see the passage tombs and museum (free and worth a stop) before visiting Ronda, Granada and Tarifa. All of these were good choices IMO.
After Tarifa. we headed back north (to be continued)...