I don't think any franchise can be totally ruined. There's always a way back.
That said, a few games pop into my head as titles that sunk a lot of momentum.
Halo 4 - 343 focused on story, graphics, and world-building at the expense of level design, AI, and engaging gameplay. Cribbing so many features from Call of Duty turned out to be a big mistake.
Resident Evil 6 - the fifth game was light on horror but provided some excellent coop gameplay. 6 on the other hand is weighed down by cinematic ambitions, and just not much fun to play.
Killzone 2 - fans are going to hate me for this but the second game moved away from what made the original great: sympathetic characters, weapons with secondary fire, multiple playable characters, diverse levels, and a gripping sci-of storyline.
Duke Nukem Forever - years of development hell turned a once subversive series into a punchline.










