The AI alone, or even in locked teams of decent groups isn't all that hard, from my experience (I'm looking forward to 1.03, AI improvements are really needed in some areas). But it's when you try to play not just a Skirmish style like in a normal RTS, but something more akin to a Civilization 4x type game with unlocked teams that things go astray.
Playing like that, how most people play a tradition 4x game, it becomes very difficult after not very long due to the AI's irrational rage at warmblooded creatures. Maintaining an alliance with even one AI player is quite hard, and inevitably you're at war with all of them, and they seem content with ignoring each other and just going after you.
There's really little point in even doing unlocked teams, because ultimately it will turn into AI vs Human, it just saves headaches and annoying mission requests to not even bother unlocking them. If you want a free-for-all type game, locking teams seems to help a bit, or just doing a locked team game.