I'd like to see them tackle a different genre. Not another turn based RPG. Maybe an adventure game with point & click segments, kinda like Beavis & Butthead on the Mega Drive. More focus on puzzle solving and exploration. I think that style fits South Park perfectly.
Plus, without a complicated battle system and not having to balance multiple classes, they could spend the development time making the game longer with more locations and explore many more episodes.
Also, no particular theme this time. Just regular Cartman, Stan, etc and during the adventure they could explore multiple themes.