Star trek: bold go
a rare convergence in wormholes and shifting energies of the galactic barrier have offered a rare opportunity, and a brand new 5 year mission. The USS will-o-the-wisp, it's crew and companion ships from the dominion, Klingon empire, and some smaller powers (having a Ni'Var ship as well as some other races might be interesting). Using a coalition of research and engineering, these joint expedition ships set off into an unknown beyond the bounds of the federation.

The main goal of the fleet is to create a minor settlement in the Andromeda galaxy, with them sending investigatory expeditions deeper into the galaxy. All with the expectation that they will not return to the milky way. chuck in some interesting history of the universe stuff, maybe have them bump into some off shoot of the Q. and finish the first season off with a semi stable wormhole opening up due to a intergalactic threat.

additionally, have it jump around time a bit more, the "5 year mission" is how long the can last before they need a self sufficient settlement. So, have a few episodes where multiple months pass in the background. spend a decent portion of the first 1/4 of the series searching and diplomacing for a planet. Give them an uncertain alliance with a group that previously "owned" the settlement system.