I've played hundreds of turns on the largest galaxy size on "Crippling" difficulty level with nine opponents and have fought very large and lengthy wars involving dozens and dozens of large fleet battles first against the Yor and then against the Drengin (very large fleet battles) without reloading or restarting. I've encountered no problems, except one minor one: when space miners run out of asteroid mines to improve, they display text below them stating "string not found" and simply stop. As a human player I am able to simply click on them and issue new orders, but I'm not certain the AI is doing this.