Big one for me: Indigo Prophecy. The plot was epic and reached an awesome peak when that acheologist revealed to you that it was some ancient Myan ritual but then the ending got a total case of the "whatever, fuck you" by throwing in aliens and ROBOTS FROM THE FUTURE.
Seriously, what the fuck?
I'm sure there are other pieces of media that have fallen apart at the end, but for some reason (possibly because I was enjoying it so much up to that point) this game sticks out as one of the worst offenses.
Oh, I do have another that I only recall because it was recent. Predators. It had some real energy and a great set-up going on (sure, cliche ridden characters, but whatever, it's an action movie, cliche is expected) and then once we made it to Morpheus' hide-out it lost all steam, the lowest point being the ending which just straight up copped out (Would have been 100 times better if the solider dude had just left and gotten blown up on the space ship ending it with the woman getting tortured by the serial killer as we pan up to more prey being dropped in.)