I was involved in a discussion on this topic on TV Tropes.
The identity of the Vasari "Enemy" was theorized to be:
1. Grey goo scenario (considering the Vasari use nanotech at the present, I doubt it. Asimov's Laws of Tool Use really put this into question. I mean, humans can imagine nanotech going crazy, why couldn't the Vasari? Unless they're stupid, there's no way it could have been an evil nanotech monster all along).
2. Green goo scenario (ie. The Flood or the Zerg, a biological counterpart to the aforementioned grey goo). Extremely overdone, particularly in video games, to the point where I'd cry foul on the originality of the concept. Starship Troopers is a fantastic book, Aliens is a fantastic movie, and Warhammer 40k is a fantastic game; but having a swarm of alien locusts just isn't as original as it once was and is frankly rather boring. However, no evidence exists to contradict this. None whatsoever. The only thing I would question is how exactly these bugs would be tracking the Vasari (or could the Vasari have been assimilated without realizing? What appears to be a migration away from the enemy is actually the scouting party OF that enemy. All of the resource sites are located and dug up a bit, all of the native races are subjugated and completely reliant on the Vasari, and there's tons of stationary structures left abandoned to infest. It's the perfect scam.) But once again, I don't favor this.
3. Unidentified sentient aliens (ie. Elder Things or some precursor race). No evidence against it, but none supporting it either. Plus, why would these guys be so mad at the Vasari? Some grudge to be chasing them for 10,000 years.
4. Rouge Advent colony. Dumbest thing you'll hear all day, I'm sure.
5. My suggestion, which was an entity that has more in common with a force of nature than anything you or I could perceive. Just imagine a supernova that's pissed off at you. That's what I think the Vasari are running from, in essence. No fighting it, just getting out of its way. Of course, there is some evidence that doesn't support this theory, namely the fact that it seems to linger in certain areas while at the same time expanding outward. "Holding territory" is a concept only relevant to a being made of matter. Something akin to a force of nature would wipe a planet clean and then move on, never considering that anything would try to come back. Unlikely, but it's what I think.
Whatever it is, it is unlikely that we'll ever find out.
I mean, it's quite a ways out, right? Perhaps the devs should make how soon it'll hit a bit more clear...