The cartoon series takes place in the same universe as Captain Planet And The Planeteers.The basis for this guess is the shared link of Tim Curry and his characters in each cartoon. We know that prior to her facial scarring and insanity, Dr. Blight was once a good-natured scientist who worked with her lab assistant/husband Malcolm to create a computer AI. After the accident supposedly took Malcolm's life and left her insane, she reprogrammed the AI into her computer MAL and gave it Malcolm's face. What if Malcolm didn't die but had also been driven insane in the accident? Pretorius sure looks a LOT like MAL, after all... and he was never given any sort of history in the series beyond the surgical removal of his own head to plant it onto a robotic body.
The mask can work in the daytime, but only when it wants to.Remember that Loki's a trickster god first and a night god second. The thing didn't work in Dr. Neuman's office because it didn't want to work at that moment. Come the Animated Series, Loki is all too ready to forgo this rule if it means getting rid of superpowered or ordinary villains. And, hey, he can wind up Lt. Kellaway day and night.
The Mask (or should I say Loki) creates several of Edge City's more outlandish villainsSince wearing the Mask effectively puts Stanley into god mode, defeating ordinary crooks is fairly easy. When he's not using the Mask, it exerts its powers more subtly by rewriting real physics into Cartoon Physics and imposing the result upon selected targets (Terrible Two; Kablamus; etc.). This is more to provide a challenge than anything; it also stops Loki from getting bored. It might have something to do with Edge City already being somewhat unhinged—the madness amplifies the Mask's powers.
Why Walter is so effective against Mask wearers.The Mask makes the wearer into a Trickster. Most Trickster-types revolve around what would make others laugh at the victim's suffering. But if someone shrugs off a prank or joke, it just isn't very funny anymore. Walter has no emotions to exploit, so Big Head/The Mask can't fight him off as easily as other enemies.