I had to think about this one a bit. I'm not usually attracted to games based on "intellectual properties" (that phrase really puts me off--it's very capitalist-lawyer speak) for some reason. Maybe I assume if I really liked the original source I won't like what they do to it in the game. Sort of like avoiding watching the movie of a book you really liked.
My first thought was the books of my favorite author, Jack Vance. Most of them have interesting cultures and settings which would be fun to game in. My first thought was his Planet of Adventure series, which is probably my favorite, but I just found out there's an old GURPS book on it which I'd never heard of before. And there's already a game for his Dying Earth novels. So for me that leaves The Dragon Masters.
The details of the setting are in the linked Wikipedia entry above, so I won't retype them all here. But you've got human clans with roughly 17th century technology and several breeds of "dragon" which are actually heavily inbred reptilian aliens. These are trained to fight, including using weapons. In the book the original aliens return to the planet to capture humans as slaves and inbreeding material and to bombard to rubble any sign of advance civilization. But a game based on The Dragon Masters would probably be better if the aliens lived on the same planet with the humans rather than descending from the sky only once in a long while. If there were several clans of humans with their inbred alien "dragons" and several factions of aliens with their heavily inbred human "servants", you could do a Game of Thrones type military/political campaign.
But it would also have the added fun of rolling up your "dragon" as well as your human character. You could have the original dragons from the book to choose from and/or a build-your-own system for the players to each create their own types. Plus, different human clans could each have their own unique set of dragon breeds to add more variety.
I'll go with The Dragon Masters for this one.