Remember to start with 16 planets as well, that way the enemy throws 16x as many ships at you with each wave and you get 16x as many ships to build. Make it difficulty 10, max out their positive handicap, build as many spire cities as you can (snake map will work best for this, I think), take all enemy planets, complete the entire Fallen Spire campaign before you take the final AI homeworld, and sit your fleet on its doorstep to intercept as many AI ships as you can before the Fallen Spire fleet gets there.
Oh, also play against two Raid Engine AI types.
I think that should about maximize your score if you have all minor factions and AI plots on.