Face off against a more advanced version of the original AI, who once again has captured the entire galaxy leaving you only a tiny planet to yourself. Then strike out and find a way to cleverly outwit it nonetheless. All the new capturables, larger fleets, and hacking abilities are sure to help. (You're going to need it.)
Or immerse yourself in a far more complicated galactic struggle involving the nanocaust, macrophages, dyson spheres, and more. Other factions each have their own goals, rules, units, and entirely unique economies. Make the scenario complicated enough and it can become "World War XV is in progress, you're in a tiny farm in the middle of it, nobody likes you, but if you can just kill that one giant angry enemy leader this will all be over."
If that sounds over the top -- and frankly that bit is wearying to us to imagine even though some people seek it out -- then take a break and maybe hack the all-consuming computer virus to be your ally, and convince the star-sized alien hives to watch your back as you take on a suddenly-less-arrogant AI.