We'll be driving from Porto to Madrid. What's the best/interesting route to take? Thank you
www.viamichelin.com can help you compare different driving options. If you wanted to go through the Douro valley, then you would detour south from Pocinho to Guarda, before turning east toward Salamanca.
If you want to drive by car, you have here a good route. I hope that you will enjoy.
http://www.routeplanner24.com/madrid-porto