Hmmm, I would say the most effective antagonists were Barzini and Hyman Roth. I would go with Roth, cus he used Pentangeli, it's clear to me that if he could use a player like Pantangeli either from the start of by manipulating the events following the bothced hit(was it botched or made to look botched?), he was Michael's most formidible foe. He also used Fredo against him to sneak people into the compound for the botch assasination. I think he was the biggest challenge to Michael.
Barzini by comparison, was using his power as the next biggest Mob-boss against Vito in the first one and it was just a matter of peeling back the layers of the onion until you got to the stinking core.
Fredo is definatly the most emotional betrayer, I would have to agree with that previous statement. Patically becasue he is so weak, he can't even keep his woman in line and in the 60's, that was a big deal, I guess. But Fredo is more of a victum, stupid, frail, weak willed as he is described it's tragic that he has to go as well.