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Dom Toretto (Vin Diesel) Appeared in The Fast and the Furious (2001), Disappeared in 2 Fast 2 Furious (2003)
You've probably forgotten that Diesel was ever not an integral part of the chicks-and-racing franchise. And the actor himself would like to, as well, confessing he regrets the confusing move. Though the sequel fared well without him, Diesel couldn't stay away for long. After making a super-brief cameo in the third movie, he came back in full force for the next four — and even went so far as to make a short film explaining his absence. He'll be back again for number 8 next year.
Jack Traven (Keanu Reeves) Appeared in Speed (1994), Disappeared in Speed 2: Cruise Control (1997)
Despite their unstoppable chemistry and that epic final make out, Jack and Annie (Sandra Bullock) didn't make it to the sequel, much to the disappointment of fans. Reeves was smart enough to turn down the critically eviscerated sequel, which took place on a cruise ship and gave Annie a new love interest. "A cruise ship is even slower than a bus," he said of his decision.
Rob Hilliard (Rob Schneider) Appeared in Grown Ups (2010),
Disappeared in Grown Ups 2 (2013)
Schneider was the only member of the original gang (Adam Sandler, Kevin James, Chris Rock, and David Spade) who was MIA in the sequel. But I think we can all agree that the real mystery here is how yet another crappy Adam Sandler comedy was green-lit — and why Chris Rock felt the need to participate again.