Before I toss my hat into the ring, I'd like to say that there are already some really top-notch answers in this thread already.
I like sf, but I do find sf gaming a lot harder to prep that sf gaming. Some of the reasons are:
1. I know, or can easily discover, what a grain mill looks like, and how it works. So, if I want to run an adventure within that space, it is easy to devise floorplans and understand the operation of the simple machine that is a water wheel. Not so for space stations, starships, etc. Heck, even running a modern game, what do I do when the players go through the restricted areas of the mall? How many of us have been in the spaces behind the stores, and know what they are like enough to describe them?
(This made the original Gamma World, which I enjoyed, hard for me to run. Running fight down a ruined subway system? Cool idea! Knowing what the non-public parts of a subway station or even a subway line should look like? No idea......Except that I do know that there are doors and side tunnels down there, 'cause I've seen 'em through the window!)
2. Fantasy is forgiving. If I take Tolkein's orcs, and toss them into the mix with Lovecraftian monsters and Gygaxian dragons, no one blinks. Lump Vulcans, Daleks, and Wookies into the same universe, though, and you can have pretty dramatic breakdown of suspension of disbelief.
3. Travel Prep. In a fantasy game, to begin I need to sketch out a village or town, the local wilderness within 5 days' travel, and a few local adventure sites. I know how far the PCs can get in their first few forays, so I need plan no farther. In the Star Wars universe, say, they can ignore my plot hook and go........anywhere. How the heck do I prep the whole bleeding galaxy?!?!!? Jump into the TARDIS, and you have to potentially prep the universe, as well as alternates, at all potential time periods. SF has a much larger "stage" than fantasy.
4. Survivability. Most sf systems are a lot less forgiving of PC missteps than D&D is. The players need not only to be able to explore the star systems they encounter; they need to be able to survive that exploration. If one phaser blast is all it takes to remove a wall, how do you design a system that both allows the wall to be removed and the PC (but not the red shirt) to survive? I have some real hope for the upcoming Doctor Who RPG in this regard, but it is difficult to have energy weapons that both seem deadly and yet the PCs can survive. There is no doubt that a lightsaber, a phaser, or a Dalek gun is more deadly than a sword. IMHO, at least.
(Same problem with radium guns in ERG's Mars series as a setting. If you can shoot someone from miles away, how does John Carter survive except by authorial fiat? And, assuming that you prefer a game where getting into a deadly situation can be....well, deadly.....how do you both give John Carter a chance to survive and make radium guns the threat they should be in that setting?)
5. Economics. I don't know about you, but a lot of my early Traveller experiences (mostly as a player) ended up revolving around economics. We traded, we gambled, we bought more and got larger starships. My PC ended up owning a luxury liner. We did very little actual adventuring, and a lot more speculation in markets. It was fun, in a way, but I'd enjoy a sf game that had a bit more of a hands-on approach to things.
6. The Law. When I kill an orc, I am fairly certain in most settings that the Law isn't going to ride up on hoverbikes and send me to the Mars Penal Colony. When I kill the slimy slug monster in a sf game, I am never really sure.
RC