Personally I would prefer smaller empires of no more than a dozen to 20 or so star systems each (total amount per galaxy maybe less than 200 or upto 150) with many planets and detailed variety of star systems (ie binary stars, blue supergiants or red dwarfs each reflecting the kind of planets it would support. Ie red drawfs would harbour a scarce amount of planets
whereas Yellow Orange type G stars would be abundant in resources and planets being that they have a higher metallicity. And please a realistic variety of moons for gas giants).
The problem with having 100s of stars controlled by computers or human players is that it becomes wholly repetitive and forgettable. I say this because I have played so many 4X Space conquest games and the latest I saw being Lost Empire Immortals and Armada 2526. I prefer each star system has their own unique feel and character with localised (outside immediate star system) anomolies like comets, kuipers belts, nebulas or black holes. Making planet conquest a completely immersive experience.
At the moment there are so few games that balance all the above out. I never saw the appeal of a strategy game featuring near infinite star systems, because the ones that tackle this rarely come on top, like Lost Empire Immortals, and Spores space stage really got tedious as well. Apparently Distant Worlds is the only one out there that tried the big numbers star system approach and claims to manage it ok. But I am yet to play it and give my honest opinion. They say its automated, but who knows if this works well.
Otherwise the only other 4X Space Strategy game that has my attention is Sword of the Stars II, I never completely gave the 1st one a chance to grow on me. But the sequel promises to introduce complex many planet star systems, with detailed terrain and points of interest (comets to name a few as mentioned in the official game interview)... and that got my attention. But its a wait and see for now.