For me, the gold standard would still be the Master of Orion & Imperium Galactica series.
Space Empires, Spaceward Ho! and Ascendancy (as well as the best Civ game, Alpha Centauri) also were good/great games back in the day. The underrated MoO clone Star Trek Birth of the Federation could also be named here.
All of these unfortunately are rather ancient by today's standards.
AI War certainly is a jolly videogame, but it's not a 'proper' 4X game (nor is Egosoft's X³).
Distand Worlds may well be the closest thing to a good modern day attempt at the genre, very much with a macro instead of micromanagement POV, but it's super-incredibly-expensive (go look up what the base game + expansions cost on the official web shop...) and the graphics, performance and tech tree all don't impress. Sadly it also has no MP mode. The game slowed to a crawl for me after a while with a very small universe, so I'm not sure if a somewhat big one is playable at all.
SOTS 1 & 2 I didn't yet get to give a fair chance, but the former at least seems awfully simplified for fast MP games. Should I skip it and go straight to #2?
Aurora I'm still scared of much like I'm scared of Dwarf Fortress.
Star Ruler's 3D universe is frankly beyond what I can wrap my brain cells around; I have no idea what's going on in that game, how to make my ships go to the right place, and what place I even want them to go.
Sins of a Solar Empire is like a really boring remake of the fun Conquest Frontier Wars. GalCiv 2 suffers from some dumb game mechanics (like how population/invasions/economy/production go together), uninteresting weapons, and a terribly bland tech tree -- which all help to ruin the otherwise fabulous ship designer.
Endless Space is a shallow rock paper scissors card game.
I guess for me the most important things in a 4X game are enjoyable research & ship design, fun (interactive) combat, and good two player multiplayer. Very few if any games have been able to provide that lately.
P.S.: Further honourable mentions of games that don't (really, or at all) count as 4X would be Space Rangers 2, Space Pirates and Zombies, Hardwar, Privateer, all games developed by Paradox (but those aren't even set in space), Deadlock: Planetary Conquest, even FTL.
Fallen Enchantress strikes me as more of a HoMM game with a slice of Civ. Warlock Master of the Arcane seems good too.
The Warlords and Imperialism games were good 4X-y games as well.
P.P.S.: I had even preordered Legends of Pegasus :/