There's a ton of buildup around the sarcophagus, Antediluvians, and the destruction of vampire society, only for it all to be le epic troll by Jack. I'm sure it's supposed to symbolize how conflict between Kindred is ultimately petty and meaningless or something, but it kind of sapped my motivation to do a second playthrough as Tremere (I chose Toreador for maximum exposition dumping).
A lot of interesting lore tidbits also ended up going nowhere, like the Giovanni family or the flesh-eater Pisha, though I suppose it's difficult to incorporate such a rich universe into one small game. Also. Mercurio is a total bro, and Ming Xiao is a duplicitous whore.