I actually think it could make a good game, but everyone in the thread is thinking about the wrong type (particularly the KotoR suggestions)
If we take away that characters, what was good about Firefly setting was the theme of this low tech rough edges western society where life was just a struggle to keep flying. Bits were always falling of the ship, travel was realtime and if you stole something you had to find someone who'd buy it.
So what we need, isn't a grand RTS or a fun RPG but something closer to a space roguelike. Have a set galaxy with lots of little planets and moons, big high tech core planets and small outposts, with less and less alliance presence as you get closer to the outposts. The game is about doing jobs, collecting people and their skills and keeping your ship afloat, I don't think you should ever actually be able to explore a planet and it'd actually be better if most of the decisions/missions/events happened very low tech, maybe when you visit a planet, it's just a window with lots of information and options and a picture of that planet. (or you could flesh it out, but it'd be harder, and the focus of the game should be on flying not walking so I think even fleshed out it shouldn't even walking around in 3D space). You discover places and then maybe you can begin to expand your outfit taking on more missions closer to the core and a bigger plothread to tie in.
No firefly characters, multiple spaceship choices and the big thing is about collecting crew (which are all very unique with special bonuses) and training them up and staying together. Imagine FTL but much easier, no restriction on movement and the crew is less expendable and more personalised.
That would work and it would be of a scale that I think it would catch on and be profitable, because it needs less money and wouldn't cost too much to buy and I think it would capture the heart of Firefly.
But FOX would never let the rights go for so little money in return. Maybe someone should just make a game like that and it can be the spiritual successor to a Firefly game that was never made