I think that he would be the most logical choice, but I read a few people say that Amazo is really the team's arch-nemesis. I like Despero, and he did cause some serious damage to the team, didn't he? I guess maybe the Injustice League could qualify? How about The Key? Has he been used in the New 52? Has Despero? I also really liked Dr. Destiny in that Neil Gaiman storyline. Who would be the League's number one villain?
darkseid makes a great foe for them, as does Lex luthor gang that had the general on it!