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.
Slither, the boss of the "Altar Ego" quest chain. He's basically a repainted, somewhat faster than usual Scythid Crawler. In other words, an extremely tiny and weak mutant cockroach.
The Destroyer, The final boss of the entire game. He's slow, has a number of blind spots, and with the proper SMG or Machine Gun can be bled to death in short order.
One-Eyed Jack if you're driving a car, as you can just run him over. You may do so accidentally, as it's possible you came screaming in in a Runner and splattered him all over the hood without even realizing.
In the Zombie Island DLC there's also a subversion in Dr. Ned, who goes down quite easily. The credits then start flying by, only for Undead Ned to rip through the credits and scream "It's not over yet!", followed by the character introduction screen "Undead Ned: HOLY F*#KING SHIT!!!"
And then played straight again when Undead Ned isn't a very dangerous boss either, despite his intimidating appearance.
Were Skag and Skagzilla can be killed in ten seconds or less. Skagzilla only needs a powerful weapon with high firing rate, while Were Skag you can use a weapon with corrode and spray it with a powerful shotgun.
In the Claptrap DLC, the optional quest boss, Cluck-Trap. It's a gag boss with as weak as all other Claptrap Mooks.
There are bosses that can be exploited due to map design or spawn point. Master McCloud won't even move from his entry spot if you die and respawn fast enough, thus causing him to stay in the same position until you leave the "corridor" to enter the "arena" and not even try to attack, but his sidekicks WILL attack you.
And the "Oh-so-hard Undead Ned"? If you enter the arena carefully you'll see him STUCK behind a rock and UNABLE TO ATTACK YOU. Once you see this, aim in his direction, keep jumping without moving and empty your guns on him.
Helob and Widowmaker are two named spiderants who you need to kill for a certain mission. You can just run them over with a runner (though the runner needs to be at full health to survive each one.)
Psychos, when they swap the axe for a grenade. Though it also counts as a Crowning Moment of Funny if said Psycho decides to whip out the grenade... at a point where it'll take more than the 3 seconds of the fuse to reach you.
The Crimson Lance probably qualify in some regards; they are by far the most dangerous class of opponents in the game due to their higher-quality firearms, higher chances of coming equipped with enhanced shields/grenades, and body armour that absorbs a lot of damage and is best worked around via Boom, Headshot, Groin Attack or Kill It with Fire (or acid)... or all of the above. Their Badass incarnations have heavy armour all over them, and can literally only be hurt by Boom, Headshot and Kill It with Fire (again, or acid). Woe betide thee if you get ambushed by one that has a Combustion Hellfire...
Drifters in Secret Armory. 50 foot tall spider-things that eat cars for breakfast. There are few things in this game that are as terrifying and skin crawling as getting your vehicle destroyed by a group of them who then proceed to whale on your sorry hide. What's worse is they don't make a sound when they spawn, see you and/or approach like everything else in the game. They do make a quiet cough-like growl as they attack, but by then it's too late.
Oh God, Drifters are frightening. They'll kill you in one or two hits when you're on foot, so naturally, your instinct is to run for a vehicle... which they can easily destroy with their acidic saliva. Oh, and using the vehicle turret's lock-on function makes the Racer and Lancer blast ineffectually at their feet. Your only hope is to be in a Monster, locked on to the Drifter, constantly firing homing missile barrages behind you as you get the hell out of there. That works fine when there's one of them... Strategic retreat.
Skags. They're annoying in the first playthrough, but manageable. In the SECOND playthrough, they become death itself, especially when Hardened Alpha Skags become common. Imagine trying to take down something roughly the size of a tank with huge amounts of damage reduction while being surrounded by lots of smaller ones who are constantly spitting Interface Screw acid at you AND others are pouncing you from all sides. Not fun.
Ensemble Darkhorse: Steve, a bandit from the trailers who's only real characteristic is yelling out "Heyyoooo!", whose popularity caused him to appear in the Zombie Island DLC and in the trailer for the Underground Riot DLC. He's even in the Secret Armory DLC as "Mini-Steve". He even appears in the sequel during a quest as an ally of the Zaford clan saying his iconic line.
Game Breaker: Playing the game is like being a bull in a china shop. No matter what, you're probably going to break something.
Go to New Haven. Note that there are five gun crates around town. Open them up. Sell anything that isn't a Double Anarchy, X4 elemental gun, or has unlimited ammo. Exit game. Load game from menu. Repeat.
And if you hold off on doing a certain storyline quest, you can claim an additional two chests.
There are a LOT of farmable red chests around Pandora. Behind Lucky's station in the Dahl Headlands is a red and two silver chests as well as one on top of Lucky's, and the enemies guarding them won't respawn as long as you don't leave the Headlands. In Rust Commons West, there are actually three easy-to-get red chests, one near the bridge, which is only guarded by a single badass bandit. Two more are at a large spiderants spawnpoint in the northwest, but the spiderants can easily be run down with the rider. Another two are in the salt flats, guarded by just two Lancers, and can be reached within 30 seconds from the New-U-Station. Hell, there's some lying around in Fyrestone, just keep quitting and loading to farm some cash.
Farming the chests in the first playthrough is only feasible once you reach New Haven. New Haven is the first zone where the really good guns (Volcano Sniper, Hell Fire SMG, Crux Shotgun etc.) can spawn in the chests.
Hunters don't even need the guns. The Bloodwing is practically a helicopter gunship at high levels.
Ditto with soldiers. The ability to hose down whole checkpoints without even being there.
A Hellfire SMG with some way of regenerating ammo for it (it's just very good if you can't regen ammo for it). About the only times you'll need something else are if the enemy is fire immune or you need range.
Combine that with Lilith's Firefly class mod, and she becomes a red headed fire-breathing death machine. And that's before you add the next item on this list.
You don't even need the ammo regeneration. Ammo is plentiful, can be dropped by almost every enemy or the various chests and stashes, and is very cheap at the numerous ammo vending machines. In addition, the SMGs tend to have a very large spare ammo capacity, at the end of the first playthrough over 1000 bullets. Equip Lilith with one of these and watch her turn everything to shreds within seconds.
The Daze status effect; particularly, Lilith's final tier Controller talent Mind Games. Mind Games gives each bullet Lilith fires a 5/10/15/20/25% chance to inflict Daze upon an equal level target. Daze reduces the enemy's rate of fire to a crawl, obliterates the accuracy, and lowers movement speed such that the effect essentially roots the target. Enjoy your easy mode critical shots.
A patch rebalanced the New Haven loot drops and the Daze effect, although now all sniper rifles do boosted critical damage.
Roland has certain class mods that have an ability that restores ammo for your active weapon. You will NEVER run out of bullets.
In fact, Roland's final support tier skill, Supply Drop, in which his turret spits out homing boxes including 10% of every ammo's max capacity at the same time, as well as 1 or 2 grenades. While it doesn't do much in multiplayer, it does mean that in single player, every time you throw out your turret (which may be often), you get at least 30% of every single ammo type and 3-6 grenades, at level one! Never rely on dirty random ammo drops again!
Don't forget his ability to heal teammates by shooting them. You will NEVER run out of health.
Add Aid Station (Turret has a healing aura) with one of the two skills that makes Roland's turret supply ammo, and he practically has his own dispenser.
Practically any given skill set is game breaking with enough points. Special mention for Mordecai's gunslinger set; revolvers were high on the kickass tier already, but max skills in things like Gun Crazy and a high proficiency means the enemies are pretty screwed.
The Hunter's Trespass ability from the Sniper Tree deserves another special mention. Five points in this allows Mordecai to completely bypass enemy shields. While "only" useful against Bandits and Lancers, it completely annihilates the end game's main enemies, the Guardians, who have very little life but extremly strong shields. With Trespass, they will die when Mordecai just looks at them.
With the fourth DLC, the last story-related quest allowes you to go and raid the Hyperion Corporate Gift shop, which happens to be a basement packed stem to stern with red weapon chests and three vending machines. Best part is you can reload your game and the chests will respawn, allowing you to farm guns as long as you want and get ridiculous amounts of money for selling what guns you don't want. You'll never need to search for decent weapons or want money EVER again.
Since game saves are unencrypted, save editors and gear construction toolkits allow some pretty severe game-breaking twinking (such as adjusting your character's skill slots or creating the rarest/best possible version of any given weapon scaled to a particular level of character).
The Clipper is one of the very first "reward" guns you'll find. It has a large clip, a high rate of fire, extra melee damage, and a chance to do fire damage. Even half a game later, it's devastating against most enemies.
Mashers. Curiously, they're actually beloved for their game-breaking power, enough that they were among the chosen few that were moved into Borderlands 2.
Lilith in general. As noted above, all characters can be built into game-breaking demi-gods, but Lilith gets special mention. Why? BECAUSE SHE CAN TURN FREAKING INVINCIBLE and stay that way as long as there are enemies around. (Phasewalk makes you move faster and enemies cannot see/hit you. You can also do area-of-effect damage as you Phasewalk, killing enemies. Yep, there's an ability which reduces the cooldown of your state of invincibility...based on killing enemies. Enter Phasewalk, kill enemies, remain in Phasewalk, do epic speed runs). Drawback: Lilith cannot interact with the environment (open doors, loot chests, jump)—but who cares if everything in the vicinity is dead? Also notable in that she can solo Crawmerax without relying on an A.I. Breaker.
How much of a game breaker is Lilith? In universe she is worshipped as a god by a tribe of bandits in the second game. Something she only kind of discourages at first.
Goddamned Bats: Rakk and scythids. These guys are cannon fodder in every sense of the word, being so flimsy they don't even have critical hit spots and pathetic attackers. You'll see how annoying they are when you're dealing with them and real threats (like bandits or spiderants) at the same time and they keep distracting your hearing with their cries and knocking off your aim.
Harsher in Hindsight: Some of the text on various Hyperion posters ("Because someone has to be in charge around here" etc.) become somewhat harsher when taking Borderlands 2 into consideration.
Hell Is That Noise: As time goes on, you'll learn the weapons have different firing sounds according to their part combinations. You have this trope in full effect whenever you hear an enemy using what you recognize is a high-powered gun, even moreso if its fire rate is high. In the Underdome matches, it borders on Nightmare Fuel.
An extremely odd variety of Player Punch, as it's a punch from the gameworld rather than a character death. Pandora being what it is, most of the other characters don't react with sorrow. You know, since the average lifespan once you hit Pandora ends up being a very small number of weeks. The game also doesn't do anything with it in terms of storyline afterwards; there's no investigation or revenge beyond immediately slaughtering another band of psychos.
The effect is diminished slightly when he's still sitting outside the building giving out quests due a glitch some players encounter. It's even more diminished when you meet Zombie T.K. Baha at Jakobs Cove during the Zombie Island of Dr. Ned DLC.
Also, Marcus in Robot Revolution. He gets better though.
Sleeper Hit: As Pitchford noted in one interview, the game actually sold better as time went on, compared to the usual pattern of a burst of sales at release, and it was all thanks to word of mouth. This is one reason why the sequel got a much bigger budget and proper advertising.
Spiritual Licensee: With the game's main focus being on collecting and playing with a seemingly endless array of brightly colored, ludicrously overbuilt guns, it's probably fair to call it the best Nerf game ever made. Especially considering the cheerfully violent and absurd story and creatures feel like the kind of things preteen boys would come up with while playing with toy sci-fi guns in their back yard.
Stop Reminding Me: No matter what you are up to, the Claptraps will keep bugging you about new missions that are available. It even gets to the point where they will repeat it AGAIN after you move to another region! The only way to shut them up is to go to whoever is offering the mission and accept it.
That One Boss: Crawmerax the Invincible, which players only attempt to kill because he drops pearlescent weapons. The developers even lampshade how hard it is by calling the mission to kill him "You. Will. Die."
Also from the Secret Armory DLC, Knoxx himself turns into this after your first playthrough (At which point his level adjusts to 2 above yours): He's incredibly strong, but the problem is that he spawns Medics to heal himself. If you die horrifically (As you easily might while trying to kill the medics before they heal Knoxx) the medics will heal him to FULL HEALTH AGAIN. After taking out the medics and going back to killing him, there's a good chance he'll spawn more Medics if you don't kill him fast enough.
Mothrakk and Rakkinishou take a ton of punishment to down (for their damage output), can deal a lot of damage quickly, and their aerial mobility means running on foot is hopeless. Even Runners have a hard time hitting them, even locking onto them. And you're given absolutely no warning about where the latter appears.
That One Sidequest: Most critter-based elemental bosses tend to be rough in the early segments of the game, but aren't required to progress. Moe and Marley and Mothrakk are the standouts.
The second Circle of Slaughter series is aneurysm-inducing unless your character either has an impenetrable shield or insane weaponry. To be fair, the first playthrough's version isn't that bad with some luck and persistence, but the second time? -shudder-
The Underdome is a HUGE pain in the ass if you play solo.
Farming Claptraps for the collection achievements in Robot Revolution. Especially on Playthrough 2.5 where you can die in the blink of an eye from being blasted from all directions by Vladof shotguns with Cheating Bastard levels of accuracy. Also, every time you die, the Hyperion soldiers come back.
They Wasted a Perfectly Good Plot: In its original, less cel-shaded version, it was to have a plot told via cutscenes, but with their art shift (they decided it'd fit their original concepts better), they throw out the story. One Gearbox member left developing games entirely due to this.
For other people, it's a subversion as many games typically have inane plots and the lack of cutscenes means the extra playthroughs aren't spoiled with redundant, seen-it-already cutscenes.
The Woobie: Dr. Patricia Tannis. Her first ECHO journal recordings paint a picture of a sociopath who cares little for her colleagues, but as the game progresses they shift to show a fairly poignant, if humorous, picture of a brilliant scientist who has thrown away her sanity in search of a mystic treasure vault that doesn't even turn out to have treasure in it. She is lonely enough to have conversations with corpses, or to hope that the violent convicts who infest Pandora will be her friend, or eventually to build an android duplicate of herself to have someone to talk to. That poor woman.
General Knoxx. Tannis is nuts, but this guy just wants to die and the rebel Claptraps just won't let him.