Unlike Laverne & Shirley and Happy Days, Mork & Mindy had already ended by the time this show premiered. So in a sense, this can be viewed as a continuation.
Although Robin Williams did voice Mork in a couple of episodes (earning a "guest appearance" end credit), for the bulk of the series the character was performed by Dave Coulier.
Besides Fred McConnell and Orson (Played once again respectively by Conrad Janis and Ralph James), Eugene also returns. He only appeared in the first season of Mork & Mindy, and is played by a different actor this time.