Raiders: A reason for there being so many. Let's say it's two-fold. First, there's an old pre-war cloning lab that was part of an experiment to create a unified, homogenous fighting force of absolutely loyal, fearless soldiers. Basically a cannon-fodder initiative, but using troops who wouldn't break, would fight to the death, and who could be grown fast. Maybe they have a drastically reduced lifespan (think Bladerunner Replicants) because of the speed at which they're grown. Basically a cross between simulants and Anubis' Kull Warriors (two nice pop culture references there).
This would tie to the Institute. Basically, rather than calling themselves mankind's saviours and all that bollocks, we'll say this was the facility tasked with creating their new super soldiers. They didn't make it in time for the war, so the facility went dark, but didn't stop the experiments. We could say it was run by a ZAX mainframe AI, and over time it realised the soldiers weren't likely to work.
Understanding that humans are frail, it went down the route of creating clone cyborgs, enhancing the frail humans with cybernetic augments, both to extend their lifespan and to make them more durable. Additionally, with brain implants the new cyborgs could be directly controlled, unlike the original human clone experiments.
Alternatively, we could say the whole idea was cyborgs from the start, and the clones were basically just the initial phase, they never got to the cyborg phase because the war happened first. That way we can say the Vault 87 clones were the older, original experiment in cloning super soldiers and wasn't actually all that successful, and the Institute clones were a followup intended to merge clones with cybernetics.
(Note, this idea can tie also to Vault 106 was it? The Gary Vault anyway. Plus, it could also tie to 87 and the super soldier experiments there, say that was a secondary, private concern, also attempting to solve the problem, maybe via alternate means).
Anyway, this leads us to the idea that the insane numbers of raiders in the wastes are the result of the ZAX AI continuing to run its experiments attempting to find the perfect combination of organic and synthetic components, releasing them into the wild in order to test viability, survivability, etc.
The soldiers are unstable, thrive in combat situations, are belligerant and unwilling to cooperate, but seem basically ok in groups among themselves. Basically raiders. We can say the cloning technology isn't yet mature (even after this long) because Motherframe can't seem to figure out the problem, hence why the clones are so unstable. Or Motherframe just hasn't bothered figuring it out yet as she's too busy messing with perfecting the combat side of things for now.
One of the positive outcomes of this could be the player convincing Motherframe to stand down and stop the experiments. But as a side effect, we could also have a morally dubious 'positive' ending where she agrees to continue manufacturing clones to use as spare parts for medical needs. This would provide medical research, parts, spare organs, all sorts, giving the Commonwealth a massive boost to overall health of its people, longevity, etc.
We can also have themes of transhumanism coming in here. Some people will be absolutely against the idea of augmenting (heading into Deus Ex territory now...), some will welcome it. Kellogg could still be a thing, giving the player their first introduction to an enhanced human (maybe not as an enemy initially, but show Kellogg going toe-to-toe with someone in power armour or something and coming out on top to show the potential power of cybernetics).
This also gives us an offshoot of genetic research into stuff like FEV. If you really MUST have some sort of enemy like super mutants, this gives a reason for their existence beyond 'lol we felt like it'. We can say the ZAX (Motherframe? Could work with something like that) experimented with a strain of the Pan-Immunity project's virus/protection/whatever to create a sturdier frame for the cyborgs, but came to the conclusion that this wouldn't actually work well beyond certain specialised needs, because the mutants were simply too big. They could work as heavy weapon platforms, but for regular soldiers or covert ops and the like, nope.
Hell, could say this is what Vault 87's gig was, developing a larger model of clone with the express intention of creating heavy weapon drones and the like. Basically another alternative, or possibly even a compliment to, power armour.
Also, if we really must have 28 days-style zombie runners, we can say these are an offshoot of the research done into the above clones. Basically large quantities of rejects, ejected into the wastes to make room (and to provide potential additional data to the Motherframe, everything helps). That also avoids the issue of utterly breaking the established lore.
We can have human types with camo skin (literally! A chameleon type natural camo dealie), hybrid types that are like Centaurs (abominations created from several creatures), suiciders (not like the FO4 ones) who are human on the surface but have some sort of biological bomb ticking away inside them (like that episode of SG-1 that introduces Cass, this'd be a nice sudden event for Diamond City rather than the silly scene where you can't talk them down or otherwise do anything meaningful). Some sort of messed up Spiderman type experiment that can attach itself to walls, ambush from above, leap tall buildings, maybe even slow the player with sticky weblike material, place traps, and so on. Lots of ideas can be applied to humans and humanlike enemies for variety, rather than... Raider, Slighty less crap Raider, Raider in power armour, Raider on drugs... *sigh*
