Well, the most annoying enemy is the prison guards on heroic if you continue to train with them until they get to the max level. They stun you every other turn.
I guess that really isn't the hardest, but they have to be the hardest first enemy in any game I've played.
Two hardest enemies for me as Psycho class was Baron Brixius and Police Colonel, the Mayor took a while but I beat him first try, Colonel took 2 tries Baron took like 5 lol as he only used Holy Scars when he was at like 10000 health and he hardly used any focus based attacks so didnt use the ability to sacrafice health for focus so it took me a good half hour to beat him.
Hardest (1st place): Blood Hounds, all the way. Way too fast, and way too strong to be considered "fair". These guys are every Psychological's nightmare!
Hardest (2nd Place): The Magical Monkey. Even against my level 28 Bio, this guy can still do over 1000 against me even when everyone else barely reaches 400. If THAT'S not too much, then I don't know what it is.
Annoying (1st Place): Gregor the ****roach. Seriously, his broken healing capabilities are extremely annoying. Got stuck as a Bio here for 3 days!
Annoying (2nd Place): Twisted Experiment. This guy was quite the chore to take down at the beggining. When he wasn't busy poisoning you, he was busy setting up his dramatic comeback (Shadow Blend + Withdrawal + Start of the game = Hax.)
Funny (1st Place): The [b]REAL[b] Hobbo. Whenever I read the description of his Buffs/Debuffs,I couldn't help but lol. One or two of them also kinda made you feel a bit sorry for him.
Funny (2nd Place): The Flower Man (I think that was his name). His Buffs/Debuffs also made me lol. What do you know, a homeless drunkard and a stoned hippie. Facing these two on a single battle would leave me with a silly grin on the face all day.
Strategic (1st Place): Almost unanimously, Baron Brixius. Nothing else needs to be said.
Strategic (2nd Place): City Council/Twin Guardians. Another nearly unanimous decision.
Fun (1st Place): Dunno bout you, but fighting the Police Colonel was actually pretty cool. Timing your healing, stunning (if possible) and attacking to his buffs/debuffs (that also added a sense of "Evil (you) Vs. Good (him)". Cool.
Fun (2nd Place): Vivian Vixen. Were-Wolf. That's all.
I'd have to say on the legend run the hound/hound/specialist, mage/mage/knight, priest/mage/knight, and hydra were the hardest. Gregor is probably the most annoying enemy (unless you're on easy difficulty where he dies way to quickly). Even though all of those were hard I'd have to say my most annoying enemy in the game was my attention span (for heroic) because I stop paying attention and the timer causes me to skip my turn (gotta stop watching TV at the same time.
The Baron. I had to do an infinite number of training fights in Zone 2 to have everything I needed. after that, I totally wiped the floor with him, so that was a good feeling.