I've dabbed in science fiction settings for Savage Worlds (see my posts on Savage Eclipse Phase for an example), and one of the resources I used was High Space. Both Eclipse Phase and High Space share a post-scarcity economy, in which most resources are much more readily available thanks to nanoscale 3-D printing, allowing most items to be created on demand and completely eliminating the need for the $500 starting equipment allowance. From there, though, the two settings are very different. High Space is a classic epic space opera setting with faster-than-light drives, starship battles, galaxy-spanning empires, and the like. The original version included a solid set of character creation rules including the concept of "cultures", which added some additional background development for characters.
High Space also provides a full-up ship design and combat ruleset, treating ships much like characters with Edges and Hindrances, which makes ship design a lot of fun. The sandbox setting itself, the Lantern, provides a lot of opportunity for adventurers to seek out the relics of lost civilizations or get involved in interplanetary intrigue. High Space is a great resource for GMs who want to run games with a Star Trek, Babylon 5, or Farscape feel. Check out the new 2nd edition at RPGNow.