Westerns. Pretty much the genre fiction least exploited by games, only really big example ever I can think of are RDR & CoJ, with a bare smattering of less prominent games from earlier eras, like Gun, Outlaws, Dust, and Wild Arms.
Game-mechanics-wise, the deadest once-big genre has to be flightsims. When was the last time you saw something like Hellcats, Red Baron, or the Jane's games top sales charts? How long has it been since a HOTAS was seen as a necessary part of any PC gamer's rig?