The Simpsons is essentially a zombie show now; It will be making new episodes long after Groening and the six main voice actors are dead.
Metroid: Other M. Didn't Yoshio Sakamoto realize how out of character Samus was in that game? She became the Bella Swan of space operas overnight. (I wonder if Dave Sim was involved in this one...)
This one may be controversial: Ronald Moore and the BSG finale. The whole series was actually our past, and they just destroy all their futuristic technology and live like cavemen, and that Hera was the mitochondrial eve of humanity. Well, what do you expect from a guy that practically made nearly everyone a cylon in the end?