Last Thursday I ran a one-shot that started with something to the effect of: "You awake strapped to a laboratory table, having been shocked into life by the Lightning. In the distance, you hear your creator shouting 'My monsters! Come alive and rescue me!' as the angry mob of villagers drags him out of the room."
I used a home-brewed system for it, which was literally made-up on the walk to the game. I had a pile of index cards. Each player designed a body part for each other player, on cards which were then given out face-down so you didn't know what your monster looked like until you looked down at your body in the first scene.
The body parts were bits from people and animals. "Hands of a concert pianist", "heart of a lover", "eye of the hawk". That sort of thing. Here's the actual PCs, as drawn by their players:
The best part was the parts. Everyone else made body parts for your character, and did so blind without anyone knowing what other parts you were going to get. We ended up with some pretty bizarre PCs as a result.
Beyond those parts, they also ended up with a set of "Eyes of a Curious Child", but instead of installing those on a PC, they used them to fix some blind NPC in the Vampire's dungeon (his name was Corwin, not that it matters).
The title of the body part functioned like a skill. Every time you took an action, you'd roll 2d6 and +2 for every body part you felt could help. ("Tongue of a Serpent" might help for sensing heat and scents, but also for tempting people like in Eden.) If your roll plus modifiers totaled 11+, you were successful.
If either die came up a "1", you'd make a tick-mark on one of the body-parts. If a body-part got 5 tick marks, it falls off. Double 1's is a tick on all your body parts, Double 6's means you've developed a soul. A soul changes your dice from 2d6 to 1d12. That means it doubles your odds of accomplishing unskilled rolls (2 in 12 instead of 3 in 36), and cuts your odds of taking tick marks by about a third.
Attack rolls were super-simple. A success killed a townsfolk, or ripped one part off a monster, depending on who was being attacked. The dice mechanics weren't amazing, but they worked well enough for a one-shot. In retrospect, modifiers didn't end up stacking as much as I'd imagined them to, so I probably should have had a lower difficulty. Dead townsfolk, by the way, became one body-part each, which basically made them into treasure.
The plotline involved rescuing the "good" Doctor Stankenfreen from the townsfolk. When that proved too easy, I added a second plot about the Vampires in the next castle over. Once you're a vamp, you're a vamp all the way. It was goofy fun, and not too deep.