How about an intergalactic colonisation story? Let's put our heroes on a huge Federation colony ship that leaves the Galaxy, headed for Andromeda, or similar. The trip will take hundreds of years even at warp so everyone gets put in to stasis for the duration. They'll arrive in the 27th century but with their 25th century level tech, and no way to contact home, we won't hear from the Federation back in the Milky Way at all. Since we are in the era of CGI - and in-universe, with no Precusors to seed this new galaxy with humanoid life millions of years ago, there will be no humanoid aliens, and no M class worlds. Maybe the Universal translators won't work on creatures from an entirely different galaxy. There'll be a whole new environment of weird planets and anomalies to explore, and new species to meet. Friends and enemies to make while trying to build a new life for themselves. Perhaps each season could be a 50 year time jump with a new generation. Let's have an El-Aurian around to provide some continuity over the centuries we cover!