SMAC/X works on W2k just fine, except for one small, graphical glitch.
In the status area where you get your messages and the power graphs, whenever the game puts up one of the info boxes of just text, it puts a "A" with an accent mark over the "A" at the end of each line. Sometimes the text overlays this character. But, if you left-click on the display, to force it to cycle through the various displays, this rogue character does not appear. Wierd.
Other than that, the game functions just fine, in both SP and PBEM/Hotseat. I can't speak to the other MP modes, as I have never played them.