At the end of March and first week of April we drove around Spain for 10 days. I usually pick up the car in Madrid, did not enter Madrid, and we went straight to Cordoba which was great. Then 3 days in Sevilla, Arcos de la Frontera, Ronda and another small village, then up to Granada for three nights. Then back to Toledo for 3 nights and Madrid for 3 nights. Did not drive in Madrid, no way. My advice is not to drive due to difficulty of parking. If you get a hotel with a spot or a nearby garage, the spaces are so tiny you better have a microcar. We had a small SUV, big mistake.
Next get all tickets for major sites (Seville Alcazar, Granada Alhambra, and Madrid Prado and Palace) a good 2 months in advance.
Watch the site you are buying on, there are booking companies that are not the museum directly. Our Prado tickets bought through a booking agent were cancelled three days ahead for no reason. I got all our tickets either through our hotel at the last minute which had some quota, or by going at 7 am to line up for the day tickets that are sold, at Seville Alcazar. They sell 300-400 same day tickets. Bring passport to buy any tickets for each person.
Our favorite town was Toledo, packed with old stuff, nice atmosphere, not so touristy or crowded. Favorite site Alhambra. Best church was the Royal Chapel in Granada. Rick's restaurant picks were all too crowded to get in. No matter, plenty of good places around.