These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
Goddamned Bats: There's a bunch of enemies that can be this, especially when they spawn in uncomfortable locations. The octopuses (who are hard to kill but touching them doesn't directly kill you) and the bubbles that the Giant Enemy Crab spits (which have semi-random movement, knock you on your ass and are more than likely to bounce you into a hole, onto some spike or onto the boss) are probably the worst, though.
That One Boss: The Giant Enemy Crab of Field 56 (SFC). Even when the platform that blocks access to the exit door is gone, it's all too possible to fall on the spikes and have to do the whole thing again. It takes three minutes and 40 seconds before it's possible to reach the door at all, and another 20 or 30 seconds before you can try and not have to get it perfect on the first try. And if you die, you have to do it all over again.
The fish posse of Field 49 can be pretty nasty too, but at least they are killable and aren't as random as the bubbles.
The Field 40 tadpole is probably the very worst, however, since there is little to nothing you can do to prevent the frogs from getting into the water. The tadpole is easy to avoid, the frogs, less so.
Vindicated by History: It was a colossal bomb when it first came out. Nowadays (partly due to Jew Wario, as well as various Youtube playthroughs like the one by Zeta Plays), it's considered one of the greatest platformers in the 16 bit era by those who know of it.