We all know Handome Jack is a pretty effective arch-villain. But he's just so damned charismatic! He'll seriously charm the pants off you if you forget that he's just plain evil! He's hilarious, and he's always got a razor-sharp witty remark for you at every turn, and you kind of shrug it off. But then he captures Bloodwing, Mordecai's (From the last game) hawk. Y'know, the one that was his special move. You go off to rescue Bloodwing in the Hyperion Animal Exploitation Preserve, and you find out that you're way too late. Jack has turned Bloodwing into a slagged elementally-driven monster against you. (And is huge.) When you get Bloodwing's hit points down to nil, Mordecai tries to save it with a tranq dart, because, y'know, they're total BFFs. o_o They are. But that's when Jack hits a button and explodes Bloodwing's head. You seethe with rage as your victory has turned into a cause for mourning as Mordecai's bloodcurdling screams fill your radio. That, my friends, is when you really start to take Jack seriously and hate him. You hate him so much. That's that memorable moment when it's not your character that hates Jack, but you. It's extremely effective.
I don't even have to list what happens after that when you go and storm Jack's tower for the Vault Key. You'll find out what major game-turner that is when you get there. But if you've already played it, then you know I don't have to say anything at all. o_o
... god damn.