2 week driving trip through southern Spain.

You don’t have any small towns in your itinerary, so nothing negative there. I will say the itinerary seems more like a check list than actually getting to know places.

I understand time constraints regarding travel, but If heading to Cáceres it would be a shame to miss places like Plasencia, Trujillo, Mérida, Zafra, and a number of the small villages and parks along the route. It was easy spending three weeks in mostly Extremadura in 2024.

You cannot miss Granada and the magnificent Alhambra. The Alhambra is one of the most beautiful sights in the world. The architecture, the gardens, the view. It's the best place to see in Spain!

You also mentioned being a hiker, and it would be a shame to pass by Caceres so quickly and not see some of the stunning natural areas in the vicinity.
I think it’s an either or decision. I found the driving very slow and not especially pleasant. I would use train unless you are really giving yourself time to explore villages and natural areas.

Caceres is definitely a gem, even if it's not really a small town. If you enjoy small towns, maybe add some small towns north and east of Caceres. Trujillo, Hervas, Guadalupe. Plasencia has a really awesome Parador. I have some old trip notes I'll try to dig up

Seville is a large city with scattered sights. Two days there (from which you need to subtract travel time) is quite short.

For me there was more to see in Toledo than in Cadiz, and I'd worry about lingering jetlag on that single Toledo day.

Extremadura is great, but I wouldn't travel that far for just one (partial) day in Caceres.

Seeing small towns in transit will cut into the days you've listed for each destination. Ronda, by comparison to the others, probably needs less time if you don't plan to take day trips from that town.