Here's our setup rule, borrowed from a game called Magic Realm (published before most of you were born)
WARNING: This may cause min-maxers in your group to go into a catatonic state and/or begin babbling incoherently about fairness, which may result in injury. I take no responsibility for any resulting injury, and gamers should consult with a professional before trying this rule.
1) choose races
2) put the requisite number of tiles in a box face down, along w/the home systems face down. Rotate around the board, with each player first deciding where to place a tile (must touch 2 other tiles if possible) - then he picks the tile, and places it without turning it face up. If it is a home system, you wont know whose it is. After all tiles are placed, they get turned over.
3) any optional tokens (artefacts, wormholes) are placed randomly by die roll after board is revealed
Every game is then different, and inequalities are usually offset by the old multi player rule that says "If you are winning we are more likely to kill you, and if you are losing we are more lijkely to leave you alone."
Using this setup, you can throw away old conceptions of what techs, races, action cards, laws, strategy cards etc are good and which are good. Because EVERYTHING will be different every game. Techs, races, and cards that you always thought sucked suddenly become gold on this map with these races in these positions.
Makes strategy MUCH more crucial because you have to be able to adapt to a new style of play each game. It's also just sooo much fun when you turn over the tiles and find the new galaxy arrayed before you