A videogame movie worth seeing?!
Well, sort of.
A bit like Reboot but with the serial numbers left on and given a polish, Wreck-It Ralph follows a videogame bad guy who gets tired of being beaten and booed for doing his job and goes to see what other game worlds there are out there.
And of course I could see an RPG version. Borrowing a joke from Paranoia, antagonist NPCs meeting at the Wandering Monster Table. Signature NPCs, maybe? Might make for a good convention one-shot.
A Jasper Fforde style fictional multiverse where characters hop from story to story or into the real world (as a discussion I had recently goes) would be more sustainable and less in-jokey (while still being plenty in-jokey).
And a game with a high enough Weird Level could take in a character who is supposed to be fictional in the game's regular setting. (Buffy gameifier CJ Carella once suggested this as a possible origin for a PC.)
Be nice to your recurring antagonist NPC. Let him do something other than wreck it.