I just recently started a Firefly game for my group and I'm using elements from D20 Modern, D20 Future and Sidewinder: Recoiled. It is really just a matter of deciding what you want to use and mixing and matching. The three books are pretty much interchangable. It really depends on what type of setting you want.
For my Firefly game, I am using the rules from D20 Future that I believe work with the setting (some that I have modified as needed) and some of the advanced classes that I believe fit the setting. I'm using a few bits from D20 Modern, including the Soldier advanced class and some of the mundane equipment. From Sidewinder: Recoiled I am using some of the equipment including a few guns that I have simply renamed and three advanced classes that I believe fit the Firefly universe very well, Gunslinger, Preacher and Sawbones. I've also managed to include information from several sources around the web, mostly stuff from Firefly fansites and the like, plus some equipment that can be found in a Savage Worlds Firefly conversion.
I think it just boils down to setting. If you want a western in space, the Modern/Future/Sidewinder rules should work well. Just pick and choose the rules that you want, throw them together and mix!