Down to one opponent left (from three), and fifty-some ships in a system is about where I end up just zooming out and watching icons on account of frame rate. Kudos to your optimization guys that I could get that far.

I know you're not looking for UI feedback at this point, but that's where I think the game needs the most work. As it is, it works, but there are four things that could make it much better:
1. Make the alert messages select or focus on the thing they're about. That is, clicking on a 'ship completed' one would select the ship, on a 'fleet under attack' message on said fleet, and so forth. So far in this game I've already built two dreadnoughts and forgotten where I put them. That number may decrease as I play more, but the easier it is to find the decisions you're trying to make, the quicker you can make 'em.
2. The List. You know the one I mean. Give us a few different ways to sort colonies; alphabetically, by number of friendly/enemy ships present, by idle construction frigates, and by idle ship construction facilities spring to mind as the most useful off the top of my head. If you add sorting, it might be nice to give the option to open a second list to allow more access to data. While I'm thinking about it, is there a way to take a stack of, for example, five ships and say, "Select three of these"?
3. A deeper rally point system. I'd give a lot for the ability to be able to say, "Build these ships, and when they're done put them into group 1." Permanent points and a manager a la GalCiv2 would be nice, too.
4. A better system for long queues. Don't change the current interface for production, because when you can keep an eye on it it works great, but give me a window that lists every place that can produce things that have a cost, and from there give me an empire-wide queue that I can fill past my current available resources.
Numbers one and two are related in that they're best for on-a-moment's-notice work. Quick access to idle production and large groupings of ships, and the ability to locate completed production quickly and efficiently are both exceptionally important abilities, and the way things are now, it becomes harder as you have more and more going on.
Three and four, on the other hand, are for setting up long-term strategies. Being able to tell four or five planets to build different parts of a fleet when the necessary resources are available, and then to have them arrange themselves into a group without human intervention, would make managing an empire with a
lot of production capacity and a lot of ships moving around all at once far easier.
Tomorrow, I attack the final AI and see how the one-on-one, massive-fleet endgame is.