Isn't the best option to make a game based on one and then add the content from other game-lines as expansions/dlc?
Vampire is the easiest system to make a game out of - mechanically. I can't even easily imagine how a Wraith game would work.
I could see Hunter - maayyybe even Werewolf and Demon integrated into a Vampire game.
Still, foisting whole new planes of existence (quite literally), entirely new mechanics into an existing game as more than a gimmick would be pretty hard.