I think the biggest factor would be how space travel works, particularly how easy it is. The easier space travel is, and the faster people can move around, the more campaign you'll have at the beginning. There will be more places to go, more aliens to encounter (as well as more aliens locally), and more alien tech to track.
If you wanted to make the campaign in D&D "start at the base town and branch out" terms, then you would want to start with slow, possibly even slower-than-light space travel (FTL oesn't have to mean instant acces, though, even at twice the speed of light it could take a year or so to move between systems). Then, either technological advances or encounters with alien tech allow the PCs to branch out and explore more things, discovering as they go.
Of course, your dilemma was more along the lines of how to design a setting, presumably with a lot of travel and different aliens and a wide scope. So, some other things to keep in mind:
-While technology will probably vary from race to race, you'll still want to decide on some basic levels of tech that can or cannot work within your universe. Every race is going to have variants on moving through space, healing disease, blasting people, etc. Some will be better than others. Where you want to set the upper limits is on things like AIs, teleportation, cloning, and other things that would have major impact on the setting. Thing about all the different sci-fi universes out there, and what they have, and decide what you would or would not like to keep. From that, you can build a sort of general picture as to how life and the game should work.
- For aliens, get a general idea of how many different species you want. There's universes out there that have only humans, and there's universes that have more species than can be counted. A middle range would probably have a few major (ie PC) species, and a number of minor ones who are mostly weird-looking background material (think of the Babylon 5 approach). This would work pretty well, since you can define 2 or 3 species at the outset and always add more later if you want to.
Aliens and tech are the major things that I can think of for starting out. Once you have that down, you can generate history (how tech was developed, who went to war over what reasons, etc) and current situations and feelings. That's a pretty good start right there.