Tell me, can anyone list specifically the plot holes created by the Prequels?
Though not necessarily a plot hole, I think that the black goo and what exactly it does has created a lot of confusion. We see it doing so many different things to different organisms that it can be hard to know what to expect from it.
It mutates people, creates embryos, spores, neomorphs, hammerpedes, and vaporizes when it hits air (on Paradise anyway) which leads to a massacre.
I've seen more posts bemoaning the "inconsistencies" of the black goo than anything else. Which is somewhat explained in the "Advent" feature when David talks about the goo being a sort of "primitive AI."