I sadly can not give many specifics, because my genetic engineering was more on the level of "heh, let's prod this thing now!", but according to what I heard from actually skilled people, half the digestive system is disfunctional.
Also, how about making toxins more realistic? Right now cyanide and ATP-decoupler are pretty much instant death sentences. You could make them potentially deadly, but survivable.
I second that the immune system could use a rework of some sorts. Some diseases are so dangerous in their current form.
While producing the 2017 genomes, I actually tried to make ATP decoupler and cyanide more fair to Creatures. But changing the bars of the genes even slightly either makes Creatures completely unaffected by the 2 toxins, or will just kill Creatures instantly again.