I can't believe how drastic the difference is, yet hadn't noticed it before. Towns felt lively enough that I didn't question it, and I don't actually pay much attention the the trains anyways so I never noticed that they'd basically disappeared from my game.
After reading through this whole thread and doing some testing myself, certain types of mods for sure are causing the issue though I can't seem to quite figure it out.
For example, the moment I popped in any ytd (textures) that were specifically for weapons (a very, very few didn't cause it that did have textures) or the players (also, very few worked); St. Denis would turn into a ghost town compared to when I'd take those out, and that was when I was running dozens and dozens of mods and scripts trying to see what I could "get away with".
In the end, spawns were getting absolutely nuked by most textures for the players and weapons, but when I would use some for random other things including a couple other peds; the spawns were correct and St Denis was full of life all up and down the streets, with passengers in trams, etc. I didn't do much testing on trains as personally it's not even something i cared much about before, and that seems to be a much deeper rooted issue than the spawning when using texture mods.
A few things I could recomend, is trying to get in contact with Dilapidated the person who made RDEs gameconfig and afaik was one of (maybe the major) driving forces behind the gameconfig discoveries in GTA V. If anyone isn't aware, GTA V has gameconfigs that support massively modded setups to play the story mods barring script mods don't break it themselves. This includes that RDE mod I mentioned, which adds tons of new police jurisdictions, an entire overhaul to the games wanted system on a script level, and multiple gigs of textures. I would imagine the core principles for editing the gsmeconfig are the same, it's just thay very few understand it in GTA V also.
Also, I haven't tried it yet, but reducing texture sizes of mods textures could help, though for some mods that's defeating the purpose. I also am not sure how to do thay as in GTA V you can extract ytds dds files in OpenIV but it doesn't seem to handle RDR2 files.
I'd love to get to use some of these texture mods, but because I have to test them I often just pass since virtually every other mod I've tested doesn't break spawns unless it's a broken mod to begin with or messes with spawns itself.