4. Scrubs, Season 9 (ABC; December 1, 2009 - March 17, 2010)
It's one thing to replace one character on a show, but when you replace the majority of them, then you're in real trouble. The final Scrubs season moved the story from Sacred Heart Hospital to the medical school at Winston University. While Turk (Donald Faison) and Dr. Cox (John C. McGinley) hung around, most of your favorite characters only appeared in fleeting appearances, if at all.
Thew ninth season of Scrubs may have been better branded as a spin-off, as those of us who were fans of the show remember feeling cheated by the final season, which made it all but impossible to enjoy.