One of the strengths of Eclipse Phase, in my opinion, is that Earth plays a minimal role in the setting. Similar settings like the somewhat disingenuously named Transhuman Space suffer from the fact that the vast majority of humanity (or transhumanity) still live on the same planet and what goes on in extraterrestrial space remains a sideshow at best.
So if one chooses to re-construct the setting without the TITANs, one still needs a way to get humanity off their old ball of dirt. But how? I'm glad you asked! Here are a few of my ideas:
1) Grey goo nanoswarm. An old classic, suffering from the fact that it's awfully clichéd by now.
2) Ecological super-AI. Shamelessly stealing the GAIA concept from Orion's Arm, one could envision an AI in charge of repairing the environment deciding that humans are more trouble than they are worth, ecologically speaking. Cue everyone except a few very pleased (at least the first week) anarcho-primitivists leaving.
3) Biocon super-AI. Similar to the above, but actually my own idea, as far as I know. If a bioconservative regime decides that human genetic engineering is a threat to liberal democracy (Francis Fukuyama), the dignity of man (insert least favorite religious nutjob here) or something along those lines, and if they end up creating a seed AI before anyone else (I could see my own dear European Union as a likely candidate - which would be a welcome change of pace from the usual "evil Americans ruin everything"-scenario) we could end up in a situation where only flats are allowed to live on Earth, everyone else being shipped off-planet to preserve the status quo. In essence, this would mean that Earth would end up as the "Jovian Junta" of the setting. Of course, nothing precludes it from being a well-functioning democracy.
So! Does anyone else have any ideas, or any comments on my scenarios?
President of PETE: People for the Ethical Treatment of Exhumans.