Don't think of it from the perspective of a gamer.
The example I like is one thagguy uses in Red Soul: Ceaseless Discharge. In-game, he's pathetic. When you apply logic to it and realize that just whapping it over and over on the arm until he dies wouldn't work, you realize that you've got a walking goddamn volcano whose vitals are all surrounded by shit that will literally melt your face off.
With the big guys, you can hit their feet over and over again and eventually they'll keel over in the games. In here, where they're not functioning on a script designed to leave openings for the player, your options are a lot more limited. Imagine if Amygdala actually used all of its arms consistently and didn't use the same motion for its laser every time.
The other key difference is this: on the human-sized enemies, it's easy to land hits to the chest and head in the game, but they treat them like any other blow. Here, a bayonet through the brain will end the fight immediately. On the big ones, you can stab them in the bum over and over in the game and it'll treat them like lethal injuries, but not here.
Gehrman is blisteringly fast and experienced, but at the end of the day, he's just a man.