It's more that changing the starting cap throws off the game balance because of the race mechanics, not so much because of the galaxy size.

Civs that colonize with ships can just claim a bunch of systems right away and those that have to wait between colonization like Hisso, Vodyani, Vaulters, or Unfallen will fall behind at the start.

It's also a big boost for races that are supposed to build tall like Hisso or Vaulters to be able to own that many systems mid game, if they manage to catch up...

Actually that might make an interesting challenge playing as Vaulters...

I should have been a bit more specific and referenced part of the actual ESG 1.6 mod tooltip which reads as follows: "However, if you are playing with more or less players then recommended, it is advised that you adjust the setting accordingly"

Capt. Cobbs (the mod's dev) gave me the answer I was looking for as follows:

"So, basically, Number of Recommend Players * 10 is the number of systems in a galaxy, and colonization cap is recommended to be something like Number of (Number of Systems / Number of Players) - 4."

"So like, Large recommends 6 players, that is 60 systems. You are playing with 4 players, that's 15 nodes per player. If you subtract 4, which is 11, that's what I'd recommend you adjust the setting to."

"I might move it back to being a multiplier rather than a flat increase in the future, which will make calculating it easier, but hope that helps."

I believe in his response he might have meant "Normal" for 6/60 and not "Large".
Large would be 8/80.

Interesting, alright. I've not used it much myself, gave myself extra systems once as Hisso and I think that was about it.