Best and worst most extreme departures long running series have taken?

[Azzanation]

BEST

I would have to say one of the best was the Donkey Kong Countries on SNES. Not only is it one of the best trilogies ever, it took a simple and basic character and made it the best.

HONORABLE MENTION

You can also add the Fallout Series, going from a strategic top down style game to an immersive fps sandbox and proved incredibly successful.

WORST 

One of the worst ill say was Alone in the Dark (360/PS3). Amazing original game and they transformed it into an unliveable RE4 clone.