What would be really awesome would be a (somewhat) realistic futuristic game set on (for example) Mars. Weapons would most probably use caseless ammunition and have very high capacity magazines, but pervasive light body armor will mostly negate that advantage. Gravity is slightly less on Mars, so people will be able to jump slightly higher. Mars has an atmosphere, so vacuum is not an issue, but oxygen is - everyone would be wearing breathing apparatus outdoors.
That's just some new equipment and some tweaks to the physics. Mars would give the game designers a great excuse to create some fantastic environments based on the photos NASA has gotten back from the various probes and rovers. It could be superb.
The campaign could be based on anything from terrorists to nativists, or both. The theme of people fighting other people should remain, however - I don't think it would be a good idea to introduce aliens.