The Mummy, which was royally screwed over by The Mummy Returns, immediately springs to mind.
Oh yeah. Evey as a reincarnated ancient princess was so stupid it took several years, Rachel Weisz's departure and a highly selective (though still ultimately mediocre) approach to continuity to continue the franchise.
X3, anyone? Killing three core X-cast members
and de-powering your main villain? I know, I know, they could bring Xavier back via the clone and Magneto's powers too somehow, but just plain undoing the two biggest events of this movie in
X4 would be almost as aggravating.
Jurassic Park III: Introduce a massive dino that no one had heard of (
right), didn't show up in
JP2 and should have eaten or killed all the Rexes by the time Grant and Co. arrived on Isla Sorna. Oh, and velociraptors talk, and are quite cuddly - good chaps, really, if you get to know them.
Episode I - giving Anakin a happy, trauma-free childhood and a loving mother pretty much ensured that his eventual fall wouldn't be psychologically credible.
Batman Begins - portraying Gotham as a modern, partly-futuristic city three or four times Manhattan's size with 1930s-style slums was so asinine that Nolan pretty much rebooted the entire cityscape for
The Dark Night.
Harry Potter 5 (book and film) - Okay, so Fudge doesn't believe Voldy's back. Are there no opposition political parties to challenge that view? Are there no parliamentary inquiries? Is there even a legislature, or in the magical community an elected permanent dictatorship? Though containing nothing
specifically franchise-killing, after four mostly fun and light introductory stories,
HP5 was the point where Rowling's intellectual vacuity could no longer be doubted or ignored. That, and it sucked wampa toes.
Golden Compass, the film - agree with the above assessment. Moving the ending to the start of the second film would have been a tonal disaster, never mind setting up a Lyra/Asriel confrontation that the rest of the movie would entirely ignore.
Episode II - the Clone Wars were
good clones vs.
droids?! You've gotta be kidding me!
@ Hermiod: I agree that
Terminator Salvation was terrible, but Connor and the resistance finished the movie pretty much exactly where they started, so I don't agree that it was necessarily a series-killer. If they made
T5, chances are you could skip
Salvation and not miss a single thing.