I was thinking of a series myself for a while.
Andromeda Galaxy a somewhat similar spiral galaxy to our milky way would a nice unexplored target.
Maybe have a new crew post Nemesis. (Enterprise E/Refit or a New Ship)
I've been trying to figure out ways to explain how they get there...
1. Worm Hole (Only Opens every 7yrs
2. A "Q" throws a ship over there to learn a Lesson.
A Empire of sorts as the main villain ebe.