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IMO, the easiest boss is the Dreaming General, located in the forest area (whatever it's called). For that, every turn, it adds "creeping roots" to two of your heroes, and hitting the tap root will remove creeping roots from one random hero. So, if you hit the tap root twice per turn and focus fire the boss with the rest of your attacks, you should be good. Heroes that can hit both ranks 3 and 4 in one attack, like the Plague Doctor with Plague Grenade/Blinding Gas, the Flagellant with Acid Rain, or the Occultist with Eldritch Artillery are extremely good here, as those both damage the boss and hit the tap root in one attack. Also, if you equip your heroes with combat items that hit enemies, such as serrated traps, you can use those to target the tap root and deal with creeping roots that way. Attacks that hit all enemies, like the Man At Arms' Bellow, also work well in this fight.
If you're using The Usual Suspects team, you could also try going after the Librarian, in the Sprawl. That fight primarily focuses on doing backline damage, so put your Highwayman in rank 2 with Pistol Shot, give your Man at Arms the Crush move, and focus fire the Librarian. Plague Grenade and Thrown Dagger are both good in that fight.
If you don't have these attacks, go to Hero Shrines in order to unlock them. Early on in the game, going to Hero Shrines is like priority #1. If you don't have Plague Grenade, unlock it ASAP by visiting a few shrines with the Plague Doctor, as it is one of the best attacks in the game on one of the best heroes in the game.
I did my "grand slam" achievement with a team consisting of Plague Doctor, Runaway, Flagellant, Man At Arms, and over the course of the 5 runs, I killed every single lair boss at least once. Though, I wouldn't recommend this team for act 2, as it is very DOT heavy and the act 2 confession boss is largely immune to DOTs. It can work though, as I made it work.
What i did just now is go straight for a lair. Either i fail and start over right away or i keep going for the map's last boss.
Anyway, here some hints:
Librarian:
1) You can kick books behind him to buy yourself some time. MAA and Leper can do it. If all of the books are burned - only miracle can save you.
2) You can remove his dodge either with items, Vestal's illumination or Highwayman's robbery.
The child:
1) Your plague doctor can cure the hunger debuff with Indiscriminate Science.
2) Better focus on the boss, ignore the meats.
3) Child hits like a truck when on first rank. Kick him away from there. Maybe lock him from the first rank with Leper's bash. Maybe lock the meat on first rank.
4) Try using Jester to dance around and block your heroes from the first rank, so they won't bite the meat.
5) Alternatively, you can lock your tank on the first rank. For example, MAA or Hellion have skills for this.
The Leviathan
1) Focus hand when it appears.
2) Buff your move resist, so there's a chance to stay above the water.
Highway Robbery can miss, Tracking Shot cannot.