Hello,
You didn't clearly state if the game you're looking for absolutely had to be MoO2-like, or if you were simply looking for a 4x game with the level of quality displayed in MoO2, regardless of the sub-genre. You already got some really good recommendations in this thread, plenty of great stuff to pick from.
First of all, I'd like to apologize in advance for my sub-par English; being somewhat of a grammar Nazi myself in my mother tongue, I can perfectly understand how a butchered syntax can deeply annoy some people, and I hope I remain intelligible enough not to irk anyone.
Anyway, have you tried Alpha Centauri? It's pretty smurfin' amazing, and leagues better than the Planetfall remake for Civ IV (although that mod is good in itself, it just doesn't come close to the perfection that was/is SMAC). The setting is Sci-Fi, the game-play is similar to Civilization, but still unique enough that it feels completely different once you're deep into it, the interface is top-notch, and the atmosphere/ambiance is unrivaled (in my humble opinion) to this day for this type of game.
Otherwise, Sins of a Solar Empire is very nice, and contains a lot of 4x elements, even though it is in pseudo-real-time -honestly, the pacing is so slow that it feels turn-based. It looks gorgeous, and it plays beautifully, so if you like your strategy to take place in deep space, you might want to look into that.
Finally (if you were exclusively looking for Sci-Fi strategy, you can stop reading here, the following ones are fantasy), there are three games I cannot recommend enough, and you owe it to yourself to at least try them out: Solium Infernum is incredibly rich and original, and takes place in the Realms of Hell, where your avatar strives to secure a position as ruling Lord amidst his demonic colleagues; the atmosphere is spot-on, the artwork superb, and the game-play is varied and unlike anything I had played before.
Secondly, Dominions 3: The Awakening just might be the best of the lot, and probably, if you get into it, the last strategy game you'll ever need. Deep, complex, extremely rewarding, with (literally) thousands and thousands of ways to conduct your godly business, it is impossible to run out of things to do here. Plus, it comes with a very thorough manual, a necessity for such an intricate game.
And, last but not least, I'm not sure if it fully qualifies as a 4x game (you do have to eXplore, eXpand, eXploit, and eXterminate), but you might enjoy Dwarf Fortress; it's pretty hit-or-miss, you'll either hate it for its horrendously awful, awful interface or worship it for its depth and addictiveness. I absolutely love it, and it is well worth a try -if you get hooked, I can promise it'll never leave your hard drive.
Voilà, I hope you find what you're looking for.
(tutorial difficulty *cough*). That Youtube introduction really helped with the fun. Plus the fact that I found a custom race configuration that I like.
