We travelled about 4 years ago (when we were first setting up home on CdA). We used P&O and travelled Portsmouth to Bilbao HOWEVER they have since shut down this route... I think the only choice you are left with is Brittany Farries (unless someone else knows better).
Our trip: 24hrs in a small cabin but there were plenty of activities/bars/cinema on the ship. We arrived in Spain first thing in the morning which was perfect for the 8hr drive to CdA (we were at the apartment by 5pm) - the worst bits were skirting past Madrid and some of the more mountainous roads we travelled (we travelled in the winter). Toll roads were lovely and quiet and made up a reasonable portion of the drive. We literally stopped for about 30 minutes in total for breaks.
Our return trip we booked a hotel in Bilbao the night before as we didn't want to risk missing the ship the following day. We also caught a big storm in the Bay of Biscay (quite common) and that knocked most people about (to be polite).
The boat that we travelled on was old and the cabins were basic... think jail cell :) however, I think the new Brittany Ship may be better.
Based on our trip you need: Plenty of cash for tolls, spare pillows and food/snacks/media for cabin, satnav, seasick tablets as well as all the basic car requirements when travelling in EU (triangles, yellow vests, GB sticker etc)!
All in all, I would definitely repeat this trip, however next time we are considering travelling via Euro Tunnel across France & Spain to see which route we prefer.