Berserk FTW
My preferred style for any AC game is stealth + hidden blade. It's satisfying to sneak into a restricted area, complete the objectives, assassinate someone/everyone, and sneak out undetected.
Then you come across a fort Captain who can't be assassinated even with a fully upgraded hidden blade. Take the captain at the Pissa Oros Citadel, for example. This is what it looks like if you're level 40, adept at combat, and decked out with Warrior abilities and Legendary gear:
https://youtu.be/4uYKwHNiA50?t=9
I'm sure that's satisfying if you enjoy combat. This is more my style:
https://youtu.be/iG64lI5uL9Q?t=26
That's the same guard at the beginning. Instead of assassinating with the hidden blade, sneak up and press depress left stick 
to hit him with Berserk poison. No fuss, no muss. The player in this video also threw in a Sleep Dart, probably so the guard wouldn't attack his allies and raise the alert level.
Leo also mentioned this on Reddit last year:
I literally only ever used Berserk to auto-takedown Giant enemies that cannot be Assassinated tbh. Never played with it, practically.
Evidently one has to visit a Blacksmith to refill Berserk. This shouldn't be an issue if you only use it for Giant enemies. I recently upgraded my tool pouch and got a free refill.
Does this method work on bosses in combat? I was hoping there was a way to instantly kill about every enemy like in the previous games. One thing I tried for easy kills was attacking an enemy from behind while they were facing a corner (punching bag technique), but that proved too difficult to make work.
Haven't played Origins at all this year, maybe this will give me an excuse to get back on. Probably mentioned this, but I was doing a minimal playthrough and didn't unlock any perks.
Does this method work on bosses in combat?
You have to be undetected. Also, it doesn't work like the hidden blade when assassinating from cover (bushes, corner, ledge). Berserk blows your cover if the target is facing you. That's what I've read anyway. I just acquired the Berserk ability and am still learning how to use it.
Update: I tried Berserk on an unsuspecting Phylakes. It had no effect.