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.
Anticlimax Boss: Lord Surtur, the Goblin King (in the days when Elf was a character class), the Master Assassin, the Dark One, and most infamously of all, Vlad the Impaler. Vlad is so anti-climatic that it's become a Running Gag to Cherry Tap him to death with -3 thoroughly corroded orcish daggers, thrown scrolls, and other such things, and name the object in question "Vladbane."
The Wizard of Yendor is this if you're properly prepared, since unlike the demonic bosses of Gehennom, he is not immune to death rays. During the final stage of the game, he will likely revive himself in front of you several times, shouting "So thou thought thou couldst kill me, fool," only to be immediately snuffed yet again by your Wand of Death. He occasionally curses your items or summons monsters while deceased, but the Wizard himself isn't much of a threat.
Medusa, despite getting her own special level, makes Vlad look like Demogorgon by comparison. Any kind of reflection will instantly kill her. If you have an amulet of reflection, she'll petrify herself when you walk into her room. If you don't have an amulet of reflection, a hand mirror will work just as well, provided you have a blindfold or towel. Alternately, smashing her in the face with a cream pie or flashing a camera at her will blind her.
Floating Eyes can be avoided, killer bees can be Elberethed, but may The Lady help you when your pet decides to start attacking that gas spore that's adjacent to you.....
On early-middling levels, you have to deal with Soldier Ants — the most common enemy-based cause of death in the game (accounting for 1.75% of all deaths on nethack.alt.org. Go team ant!), as well as mumaks, massive war elephants with a ridiculously powerful headbutt attack.
On the middling levels, you have the infamous Cockatrices and many enemies who will swallow you and kill you, including Lurkers and Purple Worms (which can also be encountered on the earlier levels).
Then you must contend with Demon Lords and Princes, and should you actually survive them and get the Amulet of Yendor, you must face an infinite amount of more and more powerful Wizards of Yendor, and the consistently respawning Riders of the Apocalypse: Death, Pestilence, and Famine. You're War.
Fridge Horror: There are lots of "used armor" shops scattered throughout the dungeons. Sometimes these shops contain cursed armor, which can't be removed, except by uncursing it or if the original owner dies wearing it. The horror comes when you realize where the shopkeeper gets his inventory.
And if you die in a shop, the game flat-out tells you that the shopkeeper takes all your possessions.
If you somehow directly steal from the shop (Teleporting with unpaid items, digging out,....), the shop owner will chase you. When you die, guess who comes for the loot?
Game Breaker: A very controversial thing to do in Nethack is "Pudding Farming", causing an enemy that splits into two whenever you attack it to split multiple times to abuse the game's prayer and sacrifice systems. A similar thing is to repeatedly kill a boss that is on the last level of the game. This boss reincarnates an infinite number of times, but gives a full score each time, meaning with the proper setup, hitting the max score is trivial (but that's OK, since in Nethack, it's generally considered a sign of skill to ascend with a lower score rather than a higher one).
The DevTeam implemented an immediate and savage punishment for pudding farmers. It's called Pudding Farming.
Also, nearly anything you'd accomplish with Pudding Farming won't help you on the astral plane.
A programming oversight with the purple worm allows you to take one as a pet, let it eat wraith corpses, and break its level cap. If you can do so, either by letting it loose in a graveyard or repeatedly reverse-genociding wraiths, you can send its level through the roof. Hit it with a wand of speed monster, keep it away from cockatrices, and it will One-Hit Kill anything that gets close. You'll have to do some work to get it through a few of the special levels, though.
Genius Bonus: Many things in Nethack, including some of its Shout Outs, are very subtle. For example, there is an enemy named the "quantum mechanic" which sometimes carries a box. Inside the box is a cat named Schrodinger's cat, which has a 50/50 chance of being either alive or dead. If you examine the game's source code, you will learn that the state of the cat is not determined until you open the box. Some fantasy items benefit you if you know the myths without even having read a spoiler: Unicorn horns heal, clay Golems can be destroyed by erasing their writing, amethysts (which literally means "not drunk") convert booze to water.
Since the game has strong Unix origins, there's also plenty of jokes only a Unix/Linux geek would understand.
In the UnNetHack variant, if you eat a long worm, the taste is described as being "spicy".
Goddamned Bats: Nymphs, Floating Eyes, and Leprechauns, to name a few.
Good Bad Bugs: If you let a tame purple worm eat wraith corpses, it will break its level cap. Exploiting this can send a purple worm's level skyrocketing.
The nethack.alt.org IRC channel is full of these people. There is a certain deference to those of outstanding achievement among the people who gravitate to NetHack and the people who created it; unfortunately, it's been festering for at least two decades now and it's to the point where you're expected to believe that people who are better at ascending are straight-up better people than you. And [your deity here] forbid that your every action does not contribute directly to ascending. note Say, for instance, digging a bunch of 1x1 tunnels off a room, making them into closets with a wand of locking, and using ring-engraved Elbereths and single zorkmids to create paths—over multiple dungeon levels—for spawned footrices to flee into said closets, thus creating a non-perishable source of rubber chickens. They got so mad. (And not a single one suggested Dwarf Fortress, despite the fact that this sort of behavior is par for the course in that game.)
That One Boss: Master Kaen (the Monk quest nemesis) and Demogorgon both qualify, as (due to his propensity for coming back with more hit points and a higher caster level than before) does the Wizard of Yendor.
That One Level: The "vanilla" version of Gehennom is often disparaged not because it is hard, but because it consists of numerous levels of tedious, twisting mazes. Variants such as Slash EM, SporkHack and UnNetHack all attempt to mitigate this by making Gehennom shorter/more varied/more deadly.