As noted, I have played a fair few Star Trek games over the years. They’ve all been about Starfleet - the FASA game supported playing traders, Klingons and Romulans, LUG at least partially did, and I did once plan a Klingon game, but Starfleet is the heart of Star Trek and we always came back to it.
I recommend the following:
Players who are cool playing Star Trek in general and the kind of Star Trek you want to do in particular. Best not to combine two-fisted space adventurers, cerebral diplomats, wannabe Klingon murderhoboes and anti-fans trying to destroy the premise from within.
Some room for somewhat oddball characters.
A ship. You could go with a base that will get a lot of visiting traffic like Deep Space Nine, but generally a ship.
A cool name for your ship, as this will probably double as the name of your series. I’ve had characters served on the Odyssey, the Valiant and the Victory, and been captain of the Horizon. Uhura didn’t want to fly on the USS Farragut and chances are neither do the players.
Some expert and other NPCs. Not too many expert NPCs. Names and looks for extra NPCs in case you need a redshirt to kill to demonstrate an alien invader’s power or an obscure expert to call up and/or kidnap.
A premise. This can be as simple as “boldly go” or as involved as “maintain the delicate peace between rival alien powers in a key strategic location after the Dominion withdraws, as a threat from before the occupation resurfaces, and keep an eye on the Klingon border...”