We have always used the ferry (Plymouth to Santander and return). There is good transport from Santander, bus or FEVE, but do check the ferry arrival times and allow for disembarking. We walked from Santander, or took the FEVE, westwards not east so cannot comment on that specifically.
One other advantage is that if you book the ferry return trip and at least 3 nights in a Brittany Ferries listed hotel then it can work our cheaper than just the return ferry fare*. Also becomes a 'package holiday' and is ABTA protected. Worth a phone call to Brittany Ferries. We booked into the Rosa Rosae in Santiago, allowing enough days after to return to Santander for our ferry, using bus and FEVE.
*Hotels do not have to be all in one place or consecutive nights, but must be booked with the ferry crossing to qualify for any reduced rate.