I haven't watched Voyager exhaustively but they had some awesome ships in there that you only got to see for about one episode (I'm looking at you, Message in a Bottle). I want the Prometheus class, Sovereign class, all that jazz
Maybe having more than one main ship/mission would be an idea. DS9 had both the station and the Defiant, and regularly had the cast spread across quadrants advancing several main storylines. That, mixed in with some high level San Francisco stuff that we don't really see in the shows (bar the occasional Skype call), could work quite well. Could have different sorts of objectives for each crew, show off more of the galaxy, and culminate in a sort of Federation civil war scenario with a mix of clashing admirals and clandestine Section 31-ery.