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.
YMMV: Cla Dun
Demonic Spider: Immortals in Cladun x2. Almost completely unkillable (and even if you have the means incredibly difficult), swarm the later areas in Trigeons, deal massive amounts of damage, some move incredibly quickly, can phase through walls and can see you from across the room. Being chased by 7+ Immortals is not a fun feeling to experience, especially with the eerie humming sound they make when they advance.
The plot-based boss enemies also usually come back as random enemies in the Rangeons, making life much more difficult since while their attacks are powered down, they're still far more powerful than normal enemies.
Tear Jerker: Some of the bad endings are actually quite tragic. Examples include Souma choosing to abandon Pudding, dooming her to certain death by the Laughter Disease, Pudding losing everything she ever cared for to alien invaders, and Sunday, Sherbet, Coco and Asagi each getting a Fate Worse Than Death.
Goddamned Bats: Many players have a least favorite enemy that, while annoying and aggravating to fight against, are not terribly dangerous. The squid enemies and the wisps who can inflict status conditions that make you heal them are some popular candidates.
That One Attack: Parchmin's ridiculous dragonbreath attack strikes an absolutely massive radius, making it nearly impossible to dodge if you're in the general direction of where he's aiming it.
That One Level: Lower-level Transitory floors are swarming with Immortals and also infested with nerfed versions of Treants and Golems - both of which have very long-range attacks that can be spammed if they initially see you walking by. In fact, it's not uncommon in later floors to be fleeing to Chaos from Transitory, even when Chaos is built to be one of the toughest areas in the game.
Game Breaker: The Divine Excess Magic Circle in Cladun x2 is generally not suited for heavy-duty postgame work due to its no-healing-allowed attribute, but apart from that it's revered with the playerbase for allowing a characters' stats to grow exponentially higher than almost any other Magic Circle there is.
Many Widened skills can become this. Kudos to Heaven Slash, which is an incredibly powerful sword skill in its own right but can be given an artifact that reduces its casting level to 10% of the normal, making it spammable.
The little-known 10% Bless tactic. Almost all spells are affected by casting level, and presumably Bless is too, but since all it does is inflict a status on the caster (Bless) that heals for a flat 50% health over time, it's incredibly easy to slap an item that reduces the casting level to a fraction of the normal amount and suddenly trying to heal back up to full health is incredibly easy and losing health is suddenly unproblematic. Unless you're using Divine Excess or another Magic Circle you can't heal, in which case this trick does nothing.
Widens and Growth Artifacts. With judicious use of Widens it's very possible to get your main character's Attack, Defense, and SP stats up to an innate 999, especially when helped along with the Ranger's Crazy Magic Circle in Cladun x2.
High-level artifacts with amazing titles in general. The first Hiyoseal, *1k, *10k, or Infinite artifact you find will be game-changing.
The infamous Title Cut 72 strategy, which involves pumping up your equipment with Fortune titles (increases drop rate) and Bliss titles (ends up making equipment only drop with better titles than the baseline titles) in order to make it so that your base drop rate is through the roof and all drops will either have no titles or incredibly good, beneficial ones.