New Crew. New Enterprise.
Make it look the best it possibly can. Give it one more layer of realistic detail than it ever had on TV.
Make the star of the show the ship and the mission.
Don't marry yourself to the characters. Tell their story, flesh them out and when their story is done let them go let someone else take over if the story demands it.
Make edgy character drama, social commentary and allegory in the usual optimistic Star Trek style.