I've had this idea for a setting and a concept floating around in my head for awhile, but have hit a mental roadblock, and maybe can get some help with it here. And before reading on, yes I have seen the show Warehouse 13 and yes this is where the idea came from:
Hidden somewhere between every work of fiction, in a secret central location, is the Vault of Maguffin: A place where if you fantasy story needs a magical blade to pierce the Dragon's heart, your Sci-fi story requires the Disk that accidentally uploads the Evil AI, or your Horror story requires the Statuette that holds Unspeakable Evil, then this is the place where all those things are stored until approved personnel (Such as your Mysterious Stranger or Rogue Computer Hacker) pick them up and place them in their required stories. However, recently some folk have caught wind of this place's existence, and by either teleportation spells or transporters, have found it. And now that they can get here themselves, they don't want to wait for the objects to be delivered to their worlds, but rather take them (At least, the ones important to them)!
From this point, I cannot decide between weather the game should be from the perspective of the people trying to break into the Vault, or from the perspective of those trying to defend it. In the first case, the players can be archetypal characters from their respective types of fiction (like knights and wizards from fantasy, hackers and spaceship captains from Sci-fi, or characters from gothic horror like vampires and vampire hunters and modern horror like slasher villians or zombie apocalypse survivalists). Though after writing up the description it could also be interesting to make the game from the other perspective, and give it a more cooperative slant.
Then I better get to work so we don't have that happen. I actually had more ideas about the players playing as the characters breaking in, as well as general concepts as to what characters were and would do (Such as a Knight being protected by armor, or the Museum Curator who's worked with strange artifacts before). After I actually wrote down the premise on paper in a fuller form and really looked at it, I though "Huh, there could also be some fun to be had in playing the security as well." It's all coming down to weather it'll be more fun as a Co-op game (as the security guards) or a competitive one (The vault raiders) and whichever one is decided upon will take the game in a different direction mechanically.