Galactic Civilizations II and Sins of a Solar Empire.
Tough for me to choose between them; GCII has a really good AI, which should mix it up for me a bit, but after playing CivIV to death, I wonder if there is anything left over...
As for SoaSE, I'm worried about how the hybrid RTS/4x feels in terms of depth/speed of play.
I like both 4x and RTS, so I'm stumped on which way to go on this one. Any advice?
Personally I love SoaSE because of the potential for modding. I got a Battlestar Galactica mod for it after I had played it to death, breathed new life into the game for me.
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