Forgive me for what is about to be a long winded post.
I am currently running a Star Trek DS9 era game using Mutants and Masterminds as the base system. Power Level 8 limits with a varying degree of PP between different crew memebers.
The system definately proved to be the best for my group. One new roleplayer and 3 3.5 players.
Now as far as story content goes I only have one big piece of advice and that is:
Techno Babble is king in Star Trek.
If someone wants to reroute the plasma flow path regulators ignition induction coil to the backflow manifold. You should let them. It might be a good idea to give them an indication of what that "modification" could do if the skill rolls fail.
I also use the Skill Challenge rule from 4th edition Dnd and I use it often, if you are not familar it is where you have to get X successes before getting Y failures.
I also try not to get into Starship battles very often. Also, since a lot of the story telling in Star Trek is character focused I would keep a list of NPC names/races on hand since star ships have crews of 100's of people. Making sure that some crew men have compelling personalities helps... Also, remember that the Doctor and Chief Engineer are the two positions that may do the most twiddling of their thumbs depending on the story content.
If you have any other specific questions feel free to post them but otherwise I am going to be sitting going on and on.