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- The BFG in multiplayer, due to the ability to fire off a shot in one room, run over to another player, and then hitscan-frag them without them even knowing. They could even kill you first, and still get nailed by the hitscan! This is all possible because the BFG 9000 is one of the most complicated weapons in any first-person shooter.
- In single player, it isn't any less powerful. Its attack covers an extremely large area & deals massive amounts of damage per hit.
- The BFG is so overpowered it turns the boss monsters into jokes, as each will die in two or three good hits (in fact the Spider Mastermind can be killed in one hit if done at point blank range), and the final boss of the sequel was specifically designed in a way to make the BFG useless against it.
- The Plasma Rifle is the first game has a high rate of fire, great damage, and fairly abundant ammunition. Point at enemy, hold down trigger, and wait for it to die.
- In a more retro tone, when a source port is used, the now-ubiquitous keyboard + mouse combo turns the original games' Nightmare! difficulty playable even by a relatively unskilled player, while Ultra-Violence becomes a walk in the park. The monsters were never coded to deal with a player as agile as they are with this combination, even when auto-aim is disabled, and are little more threatening than glorified zombies that can fire projectiles, especially when it comes to open areas. The Cyberdemon is a particularly egregious victim due to the ease of circlestrafing. Most custom maps take note of this, and scale the difficulty accordingly.
- The Artifact from Doom 3: Resurrecton Of Evil. You start the game with it and, although it doesn't do anything until after you beat the first boss, once you do it immediately becomes a Game Breaker. Then after you beat the second and third bosses it gets so game-breaking it's not even funny. Let's face it, it's hard to be afraid of the hordes of Hell when you can slow time to 1/5th of normal, run through a storm of fireballs without receiving a scratch and splatter enemies across the landscape with nothing but your fists.
- The Soul Cube is pretty damn broken, too. It homes in on the enemy with the most HP and heals you as it slices, dices and makes julienne demon slaw.
- In the multiplayer (beta), it's the Vortex Rifle. While it doesn't one-shot normally and actually does pitiful base damage, it can one shot a player, if they're less than 60 health (out of 100). Which, considering its a game with health pickups and no regenerating health, can often happen after a simple gunfight.
- The final game's multiplayer gives us the Chaingun. An automatic weapon with a good rate of fire and decent accuracy that outmatches every other automatic weapon in damage per second. Its only real weakness is its spin-up time...which is completely negated by its secondary fire to spin the barrel up at a minimal movement penalty. Its not uncommon to see half the players in any given match only using chainguns.
- The Revenant Demon Rune, to a degree. Most projectiles that the Revenant shoots, can one-shot most players, unless they are stocked on armor and health.
- In single-player, the Rich Get Richer demon rune, when upgraded, will grant you unlimited ammunition as long as you have 75 or 100 or more armor. Once you get good at dodging attacks, you can easily use this Rune to effectively grant yourself unlimited ammo and start spamming all your favorite high-yield weapons. It combines extremely nicely with a heavily-upgraded Micro-Missile attachment for your Assault Rifle, whereupon you can start creating an unending, fast-starting, rapid missile barrage with the power of the rune. Though, it does come at a price, that price being a particularly difficult Rune Trial.
- The rune also pairs nicely with the Armored Offensive rune, which causes demons to drop armor upon being glory-killed. Both runes upgraded ensures that you have a means of rapidly restoring your armor to 75 if you find yourself below that threshold if there are enemies around that you can quickly stagger.
- The Plasma Rifle's Stun Bomb (especially with with all the upgrades) + the Super Shotgun or Rocket Launcher can get any player out of a tight jam in most situations on Normal or Hard at least. The Stun Bomb can stun any enemy except bosses, and can have a player come in close with the Super Shotgun to do major damage. Or use in combination with the Rocket Launcher's lock-on or detonation mod to do more damage from mid to long distance.
- Unlocking all the Super Shotgun's upgrades will enable the player to fire off twice before reloading, allowing them to take down Hell Knights and Revenants with relative ease.
- The BFG/Ammo Boost rune combo. In this game, the BFG is just as powerful as the original but balanced out by only having three shots, and it can only be reloaded with rather rare pickups around the level. However, the fully boosted Ammo Boost gives you a rather high chance to receive BFG ammo when you Glory Kill enemies, essentially allowing you to spam the game's most powerful weapon with impunity.
- The chainsaw allows you to one-hit kill any non-boss enemy. Once you have the ammo capacity for the Praetor Suit fully upgraded, you cause use the chainsaw to easily take out the most dangerous enemies during battles, and fuel is relatively common if you keep an eye out for it.