Reducing your Empire Tree (unpinning everything and only having the very very basic you need in it), will get you the biggest bang for you buck FPS wise end game.
If you want to take it a step farther, mod the trade port/refineries ships spawn rates and spawn counts. And reduce Strikecraft squad down.
How low is up to you, but the less of these ships you have floating around end game the better.
Another thing to mod, is pirate ships. Giving them an ability to self-destruct after X time will help kill any FPS lost by the game tracking those ships.
Space elevators seemed to eat some FPS. Unless your taking pictures or video, Med settings will be great for you viewing pleasure.