Outside of things like "I want this kind of character and this kind of ship and lasers that go pew pew" the main thing I think is missing from every space-faring sci-fi RPG I've played is a genuine feeling of scale and scope. In the Fallout series, the sense of scale and proportion is palpable. You feel like your travels really are covering this enormous radioactive wasteland with its little settlements and seedy towns eking out some sort of existence. With The Witcher, you really do feel like you're working in and around the capital city of one of the northern countries. Both these games operate on different scales (TW1 being more like a large town plus outskirts whereas Fallout typically tries to represent a state-sized area of land) but the sense of scale is maintained properly in each.
Now let's look at Mass Effect. The variety of locations, the size of those locations and the implied complexity of those locations (in terms of history, culture, what lies beyond what you're immediately seeing in front of you) make the game world feel very small, yet it's trying to represent a galaxy-sized area. Now obviously it can't actually have a galaxy-sized area, but then Fallout doesn't actually have a state-sized area. The world in Oblivion is in no way as big as an actual country, the worlds in Final Fantasy are in no way the size of actual planets. However, the depth, variety and artistically created sense of scale work towards convincing the player that that is the sort of area they're operating in.
Sci-fi space games tend to fail on this count to an enormous degree. They skimp over locations which has the effect of shrinking the world. The Citadel in either Mass Effect game feels smaller and less convincing than the capital city in Oblivion or Morrowind, it feels less convincing as a bustling metropolis than Midgar in FFVII or Baldur's Gate in... Baldur's Gate. Then outside the Citadel you have near-identical featureless planets, some caves, and two other planets that feel like towns in terms of population, culture and - that word again - scope. It's not an RPG (well it could be, arguably), but X3 has a similar problem where there's no real personality or meaning to anywhere you go. Yes you could let your ship fly for hours through a black void but that's not the same as an actual sense of scale. In reality, going from London to Paris isn't that much of a distance but it really feels like you've travelled because of the differing traits of the locations, the different customs and personalities you encounter.