Twilight Princess. It wasn't a huge tonal shift, but it was an obvious attempt to pander to a Western audience that the developers didn't understand, and deliver an arbitrarily "dark" experience without any real driving force or justification. I was concerned when it was released that it was the future direction of the series, but thankfully it fell by the wayside.
The Myst series saw
UruMyst, RealMyst, and Myst 5. Real-time was a bad choice for all these games, as the Myst games released around the same time that were prerendered looked much, much better. But UruMyst and Myst 5 also saw atrocious level design.
Oh, and
Castlevania: Lords of Shadow. I understand the need to reinvigorate the franchise, but I don't see LoS as a development of the classic style as Symphony of the Night was--it's just another hack-and-slash game and doesn't have much platforming. It also has an off-putting serious tone which totally betrays the cheesy, classic horror tone of the series. Most of the previous Castlevanias didn't take themselves seriously, but for God knows what reason, the developers thought they were telling an important story with the first LoS.
The worst offense? No matter how much the games have changed, with the special exception of the N64 Castlevanias, their music has almost always tied them together. It's always fast-paced, gothic, and usually baroque in style. It helps set the tone for the different locations in Dracula's castle perfectly, and it helped set Castlevania apart from other franchises. It was a special trait that no one could take away from the franchise. They could have made all their changes to Lords of Shadow and I still would have found something to love if the music had been more like, say,
this or
this masterpiece, instead of
this fairly typical, uninteresting action movie crap.