The Pac-Man Ghosts such as the Ghost Gang are the main rivals of Pac-Man. Some ghosts were nice, but most have rejoiced in antagonizing Pac-Man. They have to be careful though because Pac-Man just might swallow them whole. They are spectral like beings that dwell in Ghost Land and sometimes the Ghost Gang and other ghosts come into Pac-Land to cause havoc.
In a cutaway in "Stuck Together, Torn Apart", Peter Griffin compares his trial separation from his wife Lois to the divorce of Mr. and Ms. Pac-Man. Three of the ghosts, Blinky, Clyde, and Funky visit Pac-Man to cheer him up afterwards. Pac-Man, who took up smoking, doesn't attempt to consume them, even after the ghosts turn vulnerable.
Brian and Stewie Griffin play Pac-Man in Stewie Griffin: The Untold Story. Brian tells Stewie to get the fruit for more points but Stewie says that he can't because there is a ghost in the way.
They also appear in a game of "Menstrual Ms. Pac Man", going after Ms. Pac-Man, who is going through her period, in "Meet the Quagmires".
Also, in "Road to the Multiverse", in one of the opening scenes, Brian can be seen playing Pac-Man with Stewie as Pac-Man and the rest of the family as the ghosts.