Help with itinerary 6 week trip mainly using trains

The Picos de Europa, Torla, and the Pyrenees would be easier to visit with a rental car. Assuming you’re going to those places for outdoors activities having a car gives you more flexibility. Those places are more remote so getting to a trailhead, for example, would be easier if you didn’t have to wait for a bus.

Every other city should be fairly well served by train or bus. None of the remaining cities are lesser places. They are all major tourist destinations.

Spain’s train website is: https://www.renfe.com/es/en and France’s website is: https://www.sncf-connect.com/en-en/. Rome2Rio may be helpful too: https://www.rome2rio.com/ but isn’t the most accurate. How about this direction:
Barcelona
Granada
Seville
Cordoba
Madrid and day trip to Toledo. Toledo shuts down when the tourists leave. I thought I would love spending the night here and was disappointed when the restaurants closed at 7p. Maybe if you get off the beaten track you can find a place that’s open but the streets were deserted too. I was there in Mar and maybe it was too early in the season. I’m not the only person who had this problem. Especially since you must transfer in Madrid to get to and from: Cordoba, Toledo and Segovia.
Segovia
Salamanca
Picos de Europa
Bilbao
San Sebastián
Torla
Toulouse with a day trip to Albi

Hi Andrea, we loved Spain! This covers several places where you’re planning to stay.

https://community.ricksteves.com/travel-forum/trip-reports/1st-time-to-spain-trip-report

We put Madrid after Barcelona because it looks like you have to go through Madrid on the train to Granada. Sounds like renting a car in Seville would make sense.

Can someone tell me a bit more about that western region north of Seville. One night stop on the way to Salamanca?

I’ll assume you’re referring to Extremadura. Sevilla to Salamanca is a 4.5 hours drive with no stops. Close to the mid-way point is the UNESCO Heritage city, Cáceres. It would be a good place to spend the night. Others cities about half way are Trujillo (home to Francisco Pizarro) and Guadalupe (Royal Monastery of Santa María de Guadalupe)

Between Sevilla and Cáceres you could make a short stop in Zafra and another in Mérida. Between Cáceres and Salamanca you could stop in Plasencia, Hervás, or Béjar. If you wanted to go off the main road you could detour over to Castillo de Granadilla and the town that was forced to be abandoned because a dam was being built. Another detour not as far off the main road in El Barco de Ávila.

It sounds as if MayPat was hoping to have dinner during the period between Spanish lunch, which ends at 4 PM or so, and dinner, which begins at 9 or 10 PM. (Personally, I really dislike the late dinner hours, but that's the local custom.) Since a great many visitors do treat Toledo as a day trip, the historic center may not have a lot of cafes that stay open and serve food through the interim period.

I liked spending multiple nights in Toledo. It gave me time to relax and see a lot of sights. I bought the little bracelet that provides access to at least half a dozen secondary sights and enjoyed the, all. The historic area is rather large and somewhat hilly, so it's easy also to spend a lot of time there, just wandering.

I also enjoyed staying in Toledo over night after the day trippers leave. In Span, we often did tapas for the evening meal. My husbands favorite tapas place was in Toledo. It is recommended in the RS guide. That place was busy with tourists and I believe also a fair number of locals all day and well into the evening.

Thanks all. We spent 3 nights in Toledo 30+ years ago, so I assumed we would spend a night or two.

We never can eat as late as the Europeans especially the Spanish and Greeks. We like to have a long leisurely lunch and have bread, cheese, olives, wine in our room later. I try to book rooms with a balcony and view.

We are intrigued about looking more closely at Extremadura - thank you jaimeelsabio. Looks like we could spend a few days exploring. Last year we spent several days in eastern French Alps and discovered a few towns off the tourist routes and loved it.