I think the analysis on Jack is going a bit too far personally. Honestly the whole game series is intentionally designed to be absurd, and Jack is designed to be as absurd as any of the other characters you run into.
The thing is, not many people wake up in the morning thinking "gee I'm going to be really evil", most people who are evil actually think they are doing the right thing from some perspective. When they aren't they tend to be too cartoonish to take seriously. Sometimes a nilistic philosophy, a desire for revenge gone too far, or even ironically love can be possible motives for someone knowingly doing something evil though. An example of the last bit would be something like "Magic Knight Rayearth" where (spoiler) the twist at the end is the bad guys are the princess and her lover who fell in love despite the princess needing to remain pure and unbiased from such feelings to hold the world together, they are literally willing to destroy the world for each other, the heroes are actually the result of a "suicide spell" cast by the princess' subconscious to bring her down so a new one can be selected to re-balance
the dying world.
The way I see it is that a villain doesn't need to be evil, and properly presented he probably isn't, he's just someone who happens to be on the other side of the equasion from you and thinks he's doing whatever he's doing for the right reasons.
Greed also tends to be a good motivator, basically when you put yourself and your own desires ahead of anyone and everything else regardless of who happens to get hurt, without even the pretensions of a greater purpose.
That said it's hard to really pick a "most evil" video game villain for me because over the years I've pretty much run into enemies who were supposed to be the little manifestation of all evil.... I mean think about what your fighting in "Diablo" for example. In D3 I literally threw the last prime evil out of heaven, and then took down the angel of death for good measure.... we're talking beings defined more or less as pure malevolence to their core.
Oh and honestly, to make a guess about "Handsome Jack" I don't think a huge amount of thought went into him, I could be wrong, but I think some people's ideas about the meaning are likely more elaborate than what the devs did. HOWEVER if I had to guess where this is going, I'd suspect something in the pre-sequel is going to give him some kind of "Chosen One" complex, and convince him he's pursueing an agenda so noble that it won't matter exactly what methods he uses in the end. Similar concepts have existed in fantasy before, and this could very well be a parody of it.
To be honest though if I was ever going to do a version of Handsome Jack, I'd probably expand the joke by finding out as he dies (or right afterwards) that had he survived he was going to be able to resurrect everyone, and nobody was going to remember it, which is why he figured "hey, why not, it doesn't matter anyway?"... but now that you killed him all the death and carnage remains, meaning you kind of just did everything he did... or at least made it matter.
But that said, yeah, I don't take Jack seriously, because as a general rule people don't go out and kill people and do screwed up shit for no reason, invariably they always have a reason and think there is going to be some benefit to doing so. Even if one uses the whole "he's just a military strong man on a screwed up planet" argument, even on Pandora there would be ways of Jack achieving his goals without going that overboard with it. What's more even if one argues he might very well have to kill the kids and stuff to eradicate some of the threats (total war) it's not the kind of thing you act gleeful about... that's the kind of disgusting crap you do when you have no choice, and always when you think some kind of greater good is going to come of it. "Kill a few now, save a lot more later" so to speak.