My vote goes to Age of Mythology. In my opinion (of course), it was superior in every way to Age of Empires. I honestly don’t see why they didn’t continue with that series (it was quite popular and got great reviews) instead of making the thoroughly meh-tastic Age of Empires III when there were games out there doing the “realistic historical strategy” genre much better by that point like Civilization and the Total War series, and the people who were just there for the gameplay had probably already moved to similar games in a different setting.
Age of Mythology had a fairly unique bit of content (you see Greco-Roman mythology and such often enough, but the way the various mythologies intermingled was cool) and the mechanic involving choosing Myth powers and the faction’s unique methods of gaining the favor resource were pretty unique. If they did a sequel there’s still a lot more they can exploit from Far Eastern mythology to African stuff to other things I probably even haven’t thought of. It also had a pretty solid single player campaign, which I like in as a player who doesn’t like multiplayer random-map battles (I hesistate to say “multiplayer RTS’s” because that excludes Warcraft 3 Custom maps which I like a great deal of) but loves a good campaign, which has really only been tackled by Blizzard RTS games, AoM, and World in Conflict.
Any other games?