The thing about CM is that it's open to so many different kinds of enemies - not unlike vanilla - except we have giant fucking guns.
Take the Vanilla cult, for example.
- Small in numbers.
- Grows through conversion.
- Ability-based.
- Corrupts the area that they loiter in.
- Share a common "head" they live to protect.
Nar'sie, a clock, standard Satan, even just the Queen Mother could all work pretty damn well. I've borderline wanted to do a write-up of them myself because of their potential (All Lovecraftian, different Old Ones for different classes).
I agree with the other commenters that I like Zombies and Necromorphs; another pair of conversion races. Same with something like Warhammer's Chaos, or Tyranids. Above-Unga Orkz? That'd be great.
Xenoids could provide a good alternative as well. They - like the cults - could just be Xeno sidegrades. More vicious, more fragile, something fucky with fire,
I would argue that the nuanced threats wouldn't work well:
Blob? Too much for one player to manage.
Changeling/The Thing? BWOINK: "Took the last angled grip" is not 'ling thing to do.
Wizard? Queens and their suites of spells are already taken-down by two people with shotguns abusing a cooldown.
All-in-all: I support anything that innovates gameplay.