3 weeks in Spain. Car/train? Itinerary

From your post it seems that you have 9-10 days already planned in Spain between Nov 8 until Nov 29. You don't mention any particular interests or other places you really want to see so it is hard to make suggestions for the remaining 10 days.

I assume we’d drive from Barcelona up to San Sebastián keep the car and explore southern Spain.

San Sebastian is in northern Spain. You can take a direct train from Barcelona to San Sebastian (5h 45m) but I don't see any overnight trains that are direct.

Maybe we should go to San Sebastián before Barcelona

There are no direct flights from Zurich to San Sebastian so fly into Barcelona.

Any thoughts on where we might want a car rather than train.

Portugal depending on where you day trip from Lisbon and take trains and buses in Spain.

In November my choice would be Andalucia - warmer and drier than other places - and a great destination. Cordoba, Sevilla, Granada easily fill 10 days, all by train, and near enough to Madrid.

I agree with Chani about Andalucia that time of year. While Sevilla, Cordoba, and Granada are all reachable by train, you might want a car to explore the "white villages" south and east of Sevilla. Maybe rent in either Sevilla or Granada and return in the other. Cordoba is an easy stop on the train route between Sevilla and Madrid. I'd recommend at least one night there, though, rather than just a stop between trains on the same day.

Madrid will be cold because of elevation, but there's lots to see there, much of it indoors. A day trip to Toledo would also be worthwhile, best done by train.

Either San Sebastián or Barcelona have high speed trains to Madrid, but from San Sebastián-Donestia it is almost double the time, so if there is a way to do San Sebastián first, given wherever you are setting out from, that would be preferred. Then fly to Barcelona. The high speed trains from Barcelona, IMHO, are great because there is not the same tedious airport time and, given that you go to Madrid Atocha, near the heart of the city in less than 3 hours, it is great. If you want to hit a few museums, etc. in Madrid, do so. I would then just take the train to Cordoba - easy walking and there is the fabulous Mezquita. Then another short train ride to Seville for the Giralda, the Alcazar, and Placa Espana. Rent a car when you leave here and hit some hill towns of Andalucia before going to Granada with the Alhambra. You could drop down the the coast and maybe drop the car in Malaga before catching a flight back to Madrid. Other routes from Barcelona would be train to Valencia (Silk Exchange, City of Arts & Sciences, Mercat Central, etc.), then a train to Seville, etc. Lots of options. (Admittedly, I am a fan of trains, but also know that on some routes (San Sebastian - Barcelona or Madrid - Lisbon), flying is the way to go.