1) The 2450 setting I have no problem with. It's far enough into the future not to be excessively bogged down by the 90's shows and their arcs. Though not specifying if the ship is in the prime/nu universe is a bit over the top. Maybe keep it vague to keep people guessing, but have a definite answer and have it revealed at some point.
2) Meh, am I the only one that thinks that as tech gets better, the ships of the line are going to get smaller and not larger? As campy as the Enterprise-G sounds, it could grow on me, but having it be some super space dreadnaught just seems excessive at best. The technobabble shuttle... why is this specifically mentioned? There's always technobabble solutions to problems, did you plan on doing something with this specific one?
3) I have no problem with the lower decks concept, but that's going to make or break the show by itself. These would have to be compelling and interesting characters with enough drive, zest and so forth to carry the show by themselves. It would be nice if the crew wasn't mostly human either. The Kirk thing is more than a little campy too. I could see an illegitimate child with his mother's name maybe and this being an interesting reveal later on.
4) You mentioned a setting, but not a story arc really. So what are those repulsive aliens supposed to do? Are they out to conquer the universe and the good guys have to stop them? Do they not give two hoots about the Federation and want them to leave? You'd need more than that to write a story.