I voted for
X-Men: The Last Stand because that's the one I'm still the most pissed about.
Superman III and
Batman Forever are both pretty crappy, but they were so long ago I'm pretty much made my peace with them.
Blade Trinity I've only seen bits and pieces of, but I'll agree that it looked idiotic (fighting vampires while listening to your iPod... WTF?!?

)
Spider-Man 3 is kind of a miss, but there's still a lot of fun stuff in there. I just look at it as less than the sum of its parts.
But
X-Men: The Last Stand... Oooh boy.
-It adapts two great X-Men storylines badly, giving neither the space or development it deserves.
-It kills off Cyclops (one of THE pivotal characters in the Dark Phoenix Saga and the most important X-Man PERIOD) offscreen in the first 15 minutes because the producers were pissed at the actor for doing
Superman Returns.
-It kills off Professor X in an idiotic way and then
doesn't even have the guts to stick with it through the end credits.
-It removes Magneto's powers. Ditto.
-It gave Halle Berry (the WORST actor in those movies) more to do just because she bitched about being underused in interviews.
-It pushed Wolverine out of the role of group rebel, in which his character works beautifully, and into the role of group leader, in which his character doesn't work at all.
-It removed Rogue's powers.
-It introduced the Angel & did absolutely nothing with him (Seriously... did he even HAVE a subplot?).
-It made Bobby Drake, one of the most sympathetic & likeable characters from the first two movies, into an asshole who cheats on his girlfriend.
-It referenced a dumb internet meme for the sake of a stupid and unfunny joke.
-And it had that creepy "de-aging" software in the opening flashback that somehow made Patrick Stewart & Ian McKellan look both fuzzy and waxy at the same time.
God, just thinking about that movie to type this post is making me angry.