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

[Salnax]

One good one: the Castlevania series starting with Symphony of the Night. For the first decade of its existence, Castlevania was a series of slower-paced action-platformers, but from 1997 to 2008, the series was dominated by a series of "Metroidvania" entries. Yet the average Metroidvania was so good that most people never really minded.