The Dark, Clenched Hole of Evil - S1.E12

Bighead and his henchmen blast Ace and Gary with a flesh ray, transforming them from animated characters to live-action ones, in which they are portrayed by Jon Hamm and Jimmy Fallon, respectively. The gun malfunctions and "unanimates" everyone, with Ed Helms playing Half-Scary, a Two-Face-like henchman, Fred Armisen as Lizardo, Stephen Colbert as Dr. Brainio, and Steve Carell as Bighead.