I’ve experienced this a few times with Amara, farming the minibosses with Joey.
Most significantly, depending on your Mayhem Level, the mobs have gobs more health than you do. So even without multipliers, a straight hit by a Yellowcake orb will down me, but just tickle the mobs.
There is a sweet spot on the damage too. Too close, like in FFYL, you’re not getting the full damage potential. Also, orb/splash damage seems to sometimes just miss.
While I farm Traunt, if it takes more than a few hits to kill him, I’ll see at least one that barely moves his shield/health. I’ve had a few situations where the first hit on my 1-shot kill build, doesn’t appear to do any damage at all. Not sure if there’s a bug or lag or what.
I have notice that when I’m in FFYL, I have more success if I aim slightly off center of the target I’m trying to kill. It’s almost as if the splash damage is better than a straight on hit. I’m sure there’s some RNG involved.