I think we might be talking about two different things here. I don't disagree with your points, I simply think that NMS has it easier because the civilizations don't really have a presence anywhere, but are actually everywhere in the game world and they don't even have to feign that there was any non-player activity going on in the locationless galaxy.But the galaxy is so big, you simply can chuck your fictional content in there. Or invent a stargate to Andromeda. Often fiction runs well with a well-known background. I do believe however that the big galaxy is hampering the story in ED when stuff just is a needle in the humoungous haystack.
And concerning the haystack, I'm a bit sceptical if there even is a metaphorical needle there to be found currently.