I recall that the AI's exogalactic affairs being a subject of an expansion. Perhaps this could be expanded upon.
My proposition:
The lobby has a new toggleable option called "exogalactic campaign" or something of the sort. This drastically changes the way the game seeds in the following manner:
The Humans start with up to two home planets (one for each former AI Home planet) with an exogalactic wormhole on it in addition to the regular stuff. It acts as a spawning point for friendly minor factions. (Enclaves, Rebels, etc.)
The rest of the galaxy is divided equally between two factions: The AI and their primary enemy, a race of incredible power such that the AI cannot crush it as it did the Humans, Spire, and Zenith.
As far as the rest of the details, I haven't thought about it much. However, everything on this setting would be significantly more powerful. The enemies use advanced tech in spades with lots of golems, spirecraft and other horrifying things. They have production facilities that produce these things directly, rather than warping them in as in the base game. This allows the humans to do direct economic damage by destroying/capturing these (heavily defended) facilities.
The Humans start out at a higher tech level, although still lower than the others so that it is still AI War in that you must lie low and take out only what you need, except that everytng has been dialed up to 11.
Maybe once one faction begins to have a significant advantage the losing side will request an alliance with the Humans to even the odds.
Obviously this is a pretty extensive change, but I think that something of the sort, if not this exact execution, would be cool.