Shackleton
Arcane
Not early in the game. Even in heavy armor there are things that still can hit you for more than your max hp.
Surely that depends on your constitution? I'm in Region 2 now and with a mix of heavy and light stuff I've not found anything so far that could one-shot me from even 2/3 HP. Some of the 'red mist' attacks take a lot off if you let them hit you but nothing unmanageable. I'm following my similar build to Nioh 1 so far, taking most stats up to 9/10 and then concentrating on whatever my main weapon is going to be, (probably Magic for Switchglaive) with a mix of Con and Sta. So far it seems a bit easier than Nioh but that might just be all my Nioh 1 hours.