I'd like to run, using D&D 3.x (with many house rules and added flavor rules from other books):
The 50 Buried Treasures of the Pirate Lord Carcasse
Beginning: The characters are pulled together by an old dying friend, who gives them the only remaining map of the 50 Buried Treasures of the Pirate Lord Carcasse, spread across the sea on various islands and in various ports. The characters must work their way on many ships voyaging to these strange islands, where hyjinx insue with the native inhabitants, feral monsters, and ingenious traps set up by the Pirate Lord Carcasse himself.
Middle: Soon enough, the characters come upon other adventurering groups, each with their own "only remaining" map of the 50 Buried Treasures of the Pirate Lord Carcasse. Suspicion, alliances, and rivalries abound as the adventurers race after each treasure.
End: Finally, the truth is revealed: the "dying old men" that each adventuring group got their maps from are a guild of immortal wizards. Only thing is that immortality isn't all that it's cracked up to be- in fact, it's boring! So they've created this entire "Pirate Lord Carcasse" legend in order to entertain themselves, sort of like Rat Race. How will the adventurers get their revenge on the guild of nigh-omnipotent geezers?