Many of the elements Shaira was describing fit into Iain M. Banks' Culture novels...
Drones are sentient, and full citizens. Ships are tremendously intelligent and participate in their own sub-culture as well as interacting with people who merely walk about. Teleportation is so commonplace that, while the Mind who is about to fling you through a wormhole is explaining carefully about the 1 in 1200000 chance you won't emerge on the other side, you lightheartedly click the "I Agree" box on the EULA and permit Microsoft Vista to ruin the computer...
Wait - that's not right.
Regardless, I agree that the interesting bits of science fiction gaming are deep under the chrome and rayguns. Hell, the "chrome and rayguns" paradigm is, what?, 50 years old now?
Let's see what happens when evolution starts taking root in technology and some bored researcher turns it up to 11.
Which 3 aspects of human existance do we want to radically change for the setting?
Intelligence / Cognition?
Reproduction / Longevity?
The Human sensorium?
Human's place in the cosmos?
We'd also have to define Humans' place in the culture found in the new environment.
What specific things do we want to tinker with? How do these changes interact with each other?
Too many things, and you run the risk of a setting that's too alien for most gamers to invest in. Too few things (or not developing them deep enough), and you are in danger of seeming cliche.
This thread's very interesting...