Putting the awful enemy AI aside, even just in terms of design and story I thought Colonial Marines pushed things way too far there.
I'd be more interested in visiting a lab that was experimenting on Aliens and yielding all kinds of weird mutations a la the Newborn or the Neomorphs or the various Prometheus creatures than I would be in seeing dozens of Aliens that just have these radically different builds and "attack modes" solely for the sake of gameplay. But then, the random Aliens in Colonial Marines are just one symptom of a much larger problem that all trickled down from someone deciding that it would be a good idea for Hadley's Hope to still be standing.
Utilizing the pathogen from the prequels in the game would be a good way to get some weird genetic offshoots in there and up the enemy variety, I think.