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.
Game Breaker: One of the abilities you get later in the game allows you to grind upon rails and wires, which also refills your electricity and health. And the rails and wires are numerous, meaning you're fairly set. The developers probably noticed this, hence why the sequel severely depowers the grinding and railing, no longer allowing them to recharge your health and electricity, save using the poles they're attached to.
Snipers. You'll often find yourself peppered with gunfire from above when you're exploring an area on the ground (yet another reason to take to the rooftops) and their attacks can whittle away your health while you're trying to focus on guys with rocket launchers or Conduits.
They're extremely annoying when you're doing something else, too - walking around, minding your own business, then BAM! A bullet to your back. The gunfire often draws in nearby mooks, too, and with Dust Men or First Sons, they'll call squads of six or more flying at you like some sort of annoyance squad.
If you're playing Evil Cole, the rock-throwing civilian mobs can be like this, since it's difficult to tell where the rocks are coming from, the throwers don't show up on your radar as hostiles and apparently the city is stocked with dozens of people who could've made a career in the Major Leagues, hitting Cole from the better part of a block away. And to make it worse, in what seems to be a kind of glitch, if you get too close to the mob, some of the members will attack you with their fists, which has the same effect as being attacked by the civilians infected by Sasha's tar, meaning that you can't fight back or do anything other than run for several seconds.
And then there's the grenade-launching flying drones that the First Sons use, which also are able to turn invisible. It can be incredibly frustrating to destroy these as they fly about rather quickly, meaning Precision is the only reliable method of killing them, despite how much energy it uses.
Moral Event Horizon: If you choose to activate the Ray Sphere a second time when given the chance, you become more powerful. However, you kill a lot of people in the process, and your Karma Meter is set to "Infamous" permanently.
The Scrappy: Trish, due to the fact that she treated Cole like shit despite it being obvious that Cole didn't activate the Ray Sphere on purpose. Yes her sister died in the explosion but that's still no excuse. Many fans were actually glad that Kessler killed her.
Moya. She's a cold-hearted slut who has no regard for Cole's life or safety, lied about being John's wife and makes it clear that the only thing she cares about is getting the Ray Sphere before the government does, presumably to use for herself, all while painting herself as The Woobie despite being devoid of any redeeming qualities.
"Secrets Revealed". For God's sake, Moya, why did you ask a man on foot to chase down a goddamn helicopter?!?
"Anything For Trish", essentially an escort mission where you're escorting a gigantic target that can't dodge. Unless you jump off to handle each enemy group as it appears, you can get overwhelmed very fast. Making matters worse, while Cole would do anything for Trish, the player is unlikely to feel the same at this point, though she does get better from here. (Of course, that's only a problem in the Good Karma route — Evil Cole deserves all Trish can dish out.)