If we're talking about generic, non-characterized characters, then, by far, my least favourite enemy is the Regenerators from Resident Evil 4.
First of all, their breathing is less scary, more an indicator of, "God Dammit, now I've got to waste another 200 of my TMP bullets that I've been saving".
I truthfully couldn't get past them the first time I saw them, and decided to not read any FAQs. Thankfully, I finally read that memo Luis left, saying that I needed Thermal gear to see it. I asked a friend, and he said that you had to purchase a certain upgrade for the rifle for that.
When i heard that, I kind of gave up on Resident Evil 4 for a while, because 1; I didn't have enough free (not from equipment) money lying around to buy this, and 2; I didn't want to waste so much ammo on the first few I fought before i got the upgrade.
Maybe I'll try to play it again and maybe just run away from them. They are quite slow, anyway.
IF we're talking about Characterized Characters, then my least favourite Antagonist is Alexander Leland Cayne from Hitman: Blood Money.
If you don't know who this is, this is the guy who is in the wheelchair, blue-balling the reporter on how many times he "Killed" Agent 47.
I kind of hate the way how every mission began with a cut-scene of him saying something like, "... and then we found him..." or "... And the perfect trap was set...", making me double paranoid of everyone, and thinking that, out of no-where, an agent would attack me(like the "Terminal Hospitality" level in Hitman 2: Silent Assassin, when, at the end, you get ambushed by one of you clones).
I probably thought too much into this, since nothing really happened, especially at the mission when you meet him, and he says, "Let's have a duel: You and me. Come to (x) location so i can have my revenge". I checked on of the hints that you can purchase, and it says, "Don't Trust the Devil", which told me that this guy, who in this level was dressed as the Devil, shouldn't be trusted. So i simply killed him right away, kind of ruining my stealth rating, figuring out that he actually just wants to duel you.
His arrogance was un-refreshing, he somehow survived 50 or so bullets to the face, and he runs away at your own funeral. This man deserved to be handicapped (and no one really does).