I think we would have to add more than just a space setting, despite how awesome it will be , because people may get bored looking at the same scenery for 20 levels. ( Case closed anyone?? )
But, I have thoughts: you know when gordon launched the satellite in half-life? Maybe something went wrong with it or associated space station, whilst he was gone, that he's gotta fix. Also, the bit in the end sequence where you see all the destroyed tanks and F-16s in Xen? Didn't the g-man mention something about humans having taken control of the border world? This gets me thinking, it could emerge that there has been a huge attempted invasion of Xen that has gone deeply pear shaped, and now the world has become the battleground. New York looking like stalingrad and all that. The g-man could have a secretive role as perhaps being the mastermind of all this, or maybe playing off the aliens and humans against each other, for some sort of personal gain...
Also lets not forget the other aliens from opfor who, correct me if I'm wrong, are also enemies of the Xen aliens. They could play a part.