My favorite (and I think our group's) one-off was a game in where everyone, save for one player, played a half dragon PC that had been brought together to rescue one of their parents. The non half dragon PC was a spy/traitor that sought to kill the parent dragon. All along their journey, I crafted a subtle chance for each of the other party member's to discover the traitor's intentions. The traitor died at the end, but killed off nearly half of the party before he did. They still talk about that game to this day.
The other idea is one which I've always wanted to run (saw on this board many years ago), and works best if you have some good min/maxers in your group: tell your group to roll up characters, but they have to select a monster race . When they arrive to play, swap their rolled up monster PCs for your pre-rolled PCs and make "their" PCs the villains of the adventure.