I've run several Champions games based on specific comics. (I once had the super-team spending over an hour real-time fighting what they thought were super-powered aliens attacking earth, before they discovered that they had blundered into the origin of the Fantastic Four.

Once I had a C&S knight who found a magic ring, which turned out to be one of nine rings made for men by a Dark Lord.

Someday I plan to run a D&D game in a land of ruins and the dregs of an ideal medieval society, and they will eventually discover that it's fifty years after the fall of Camelot.

I'm currently playing a 2E D&D loosely based on the colonization of America. In the first couple of sessions we rescued the Roanoke colony.