Most of their human villains became less human and more grotesque as the title went on:
-Dr Destiny: A normal human inventor with a human appearance, over time with his use of the gem and machine to invade dreams, he became to waste away and looked less and less human. He was wasted away to a skeletal appearance even before Gaiman worked him into Sandman. Even before Sandman he had those horror villain elements to him.
-The Key: another normal human inventor using gagets and psychoactive chemicals. He was accidentally exposed to his own radiation by John Stewart which left him in a dwarf like state then he found out he only had a few years left to live which lead him to try to kill the JLA twice. The second time, Zatanna gave him part of her life force so he wasn't on the verge of death. Post Crisis, a revamped version of him returned where he looked more psychotic and inhuman looking.
-Professor Ivo: Creator of Amazo and had a terrible phobia of death to the point where he didn't attend his own mother's funeral. He specialized in building androids and one adventure left him looking gross and mutated his face into half human/half animalistic appearance. He kidnapped several people including Black Canary in order to use them to make himself look human again (I forget the exact details but that was his goal). He is also the only one who successfully managed to kill JL members; he killed Vibe and Citizen Steel from JL Detroit effectively closing the book on the Detroit era and the final villain of JL vol 1. He was also completely out of touch with reality in that story arc.
Conclusion: fighting the JL long term is bad for your health.
I wonder if anyone else, writer or fan have picked up on this?