In the interest of moving things forward, I think picking an existing setting (possibly tweaked) is the way to go. Here are my thoughts on some of those:
Just No: These are all fun to watch/read, not fun to play or don't really work for an RPG for various reasons.
Sure: These offer a lot of avenues for a game to explore and aren't completely dominated by a single character or event (except mass effect). They also offer a combination of technological capability and level of expansion that I appreciate. Things are fairly well settled, but there's also plenty of space left to explore, and exploring doesn't take generations. I don't think it's a coincidence that these are all games already.
Elite/Evochron/Freelancer/X series, etc
Firefly. I'm not a fan of how long it takes to get from place to place in Firefly. I also don't like how contained it is. However, these are not show stopping issues for me. In particular, I prefer my space fiction to have some form of FTL travel in it.
Cowboy Bebop. I'm not a fan of how contained everything is. On the other hand, the ruined but still accessible Earth is somewhat appealing. I'm also not sure if Bebop has FTL travel, or just very fast sublight with relativity handwaved away.
Farthest Star. To my knowledge I don't think this exists enough to give us the common base of knowledge and assumptions that makes using an established setting worthwhile. Otherwise I have no problems with it.
My thoughts regarding other issues that have been brought up:
System: I like FC more than 2.0, but I also think that 2.0 is generally better suited to this task and porting FC is probably more work than it's worth. So I guess either is ok with me, but 2.0 is the smarter choice in my opinion.
Magic, or whatever you want to call it: Meh. I can go either way. This should probably be determined by the setting we choose, and whether said setting has this or not makes no difference to me.
Hardness of the Science: I prefer my science harder than not, but there are some things it's easier not to deal with. For instance, if there is some FTL in the setting, I would prefer it be a method that is not definitely impossible or rely on what is essentially magic (hyperspace). That said, relativity is a pain, causality is a bigger pain, and time travel is just completely unworkable in my experience.
Transmechs: Uh.... I hate to rain on people's parades, but I don't really feel good about transformers, or giant robots in general. I'm just fine with regular robots, androids, cyborgs, AI in strong and weak varieties, and probably other things I'll think of later. But, I tend to get put off by things that Michael Bay gets excited about.