I rode from Santander to Valencia earlier this year via the Picos, Segovia, Cuenca. I stayed off motorway entirely and found Spanish A class roads superbly surfaced and little trafficed.
Garmin routefinder lists the shortest direct non motorway route from Santander to Valencia as via Burgos, Soria, Turuel as 417 miles taking 11 hours.
The fastest route is stated as via Burgos linking onto the motorway for Madrid then cutting across to Valencia. Listed as 468 miles 8 3/4 hours run time.
I have ridden these sort of distances in a day but would tend to take the short route and do it over 2 days as this will be much more scenic and you are on holiday! November days will also be shorter & you may not want to ride on into the night.
The Picos are very close to Santander and well worth a day or two before you return.