Here’s a list of ideas I came up with this morning: (Maybe one of them will inspire someone?)

YOU ONLY GET ONE… Bullet, your worst enemy is suicide (see “The Consuming Shadow”)
YOU ONLY GET ONE… Bullet, it’s a puzzle game, and you have to ricochet the bullet.
YOU ONLY GET ONE… Gun, and you have to earn other guns from enemies (CS Gungame).
YOU ONLY GET ONE… Enemy per room.
YOU ONLY GET ONE… Inventory Slot (Hotline Miami?).
YOU ONLY GET ONE… Umbrella, also you’re a cat and it’s raining.
YOU ONLY GET ONE… Second to beat levels but you can slow down time. (My favorite)
YOU ONLY GET ONE CHANCE… to make a 48 hour game.