Couple of nice long days
The main roads Palencia-Valladolid-Salamanca are dull dual carriageways and the minor roads are crap, at least as far as Valladolid, after which there are at least a couple of options. Main road south from Santander towards Palencia over the mountains is also busy, loads of trucks. Depending on time available, I'd recommend some more windy stuff. Try going west a bit to San Vicente de la Barquera and south through the Picos on the Riano road, weather permitting. Check before you travel, but it should be OK ish at that time of year. The pass is high, over 1600m, so it can be a bit inclement. Worth it though, if not. But it'll add at least 3-4 hours on your travel time to Salamanca
You can then continue due south on the N621/N625, skirting Leon, and thence cut down through Zamora towards Salamanca. Hard to find an interesting road on the
meseta in my experience, although they must exist somewhere!
From Salamanca south you have to cross another fairly high mountain range to get into Extremadura, the Sierra de Gredos. There aren't many roads so just pick a main one.
South from there is beyond my recent experience I'm afraid, I rode a lot of the more northern stuff a number of occasions on the way to visit me bro in Lisbon, but not crossed Extremadura North-South meself. Plasencia-Caceres-south seems to be the obvious route
Have fun
A few pics off the Riano road over the Picos - ignore the fat git doing the Ted Bovis impression
