As Woodman says, the 4Xs refer to the typical flow of the gameplay in these types of games. First you explore the world around you, then you expand into it to build new cities/colonies/etc., then you exploit the resources you've acquired during your expansion, then you exterminate your opponents. :)
And yeah, comparisons with MoO2 are tough. They're both great games, and Distant Worlds deserves to stand right up there with the Orion series. It's greatly changed how I think space 4X games should be done. If you'd asked me a few years ago, I'd fanatically tell you that if it wasn't turned-based, with separate turn-based tactical battles, I wasn't interested. Now, after Distant Worlds, I want more developers to go the continuous-time route. It's a very natural fit for space 4X.