Plot hole: When Peyton/Darkman is showing Bridget how the liquid skin works, he drips a small amount onto his burnt finger, and it solidifies. However, when he drops it onto his finger, it magically shapes itself into a replica of a perfect, undamaged finger. This makes no sense, as it is simply a liquid and is not being molded by any forces. Hence, it should not look like a perfect finger.
Continuity mistake: When the industrial plant explodes at the end of the film, as Peyton and Angela/Jenny escape, in the wide shots you can see the flames are so big, that they actually set the actors on fire. However, in closer shots, not only are the actors not on fire, but the explosions are much smaller.
Other mistake: When Peyton/Darkman returns to his home, you can see that most of the footage of him arriving and experimenting in his lab is actually repeated footage from the second film, mixed in with some new footage.
Continuity mistake: When Rooker has his gun pointed at Westlake during the climax, watch closely. Throughout the scene, he's holding his gun sideways in a side grip. Right after he says the line "I don't think you'll be needing that anymore, doc!", he rotates the gun upright into a normal grip. However, in the very next shot, he's once again holding his gun in a sideways in a side grip. (These shots are back-to-back, so there's no way he was able to rotate it again between cuts).