First, this page needs to mention slowbeef, creator of the idea of Let's Play-ing in video form.
Helloween4545's playthrough of F.E.A.R., specifically when he learns how to shoot grenades in midair and one-shots Replicas with flying kicks.
A cooler example is in his LP of Dead Space, when he's ambushed on the bridge by a bunch of Necromorphs. He uses the alt fire button for the pulse rifle he's holding. Isaac crouches down and part of the gun begins to spin, firing off shots in all directions. As ineffective as it is, it still looks awesome. Not to mention that he took down the first Brute he encountered while taking no damage.
Coestar, a Mine Craft LPer, Colonized HELL in a mere 15 videos, and his attitude was "yeah, typical tuesday in hell, meh" for episode 7 or so onwards. He found hell kind of boring. HE FOUND HELL BORING. HOLY SHIT PEOPLE.
In the Spoiler Warning one year anniversary, while playing Amnesia: The Dark Descent Reginald Cuftbert/Jack manages to "defeat" one of the terrifying monsters by standing upon its head and making it his personal mount. And most of them aren't freaked out by this game.
Medibot gets one during Wolfshirt's Dungeons and Dragon's let's play. He has his character Miriam powerslide over to one of the enemies and rap at him so amazingly that the DM counts it as an attack of his choosing.
You may not expect to find one in a cutesy game like Kirby's Epic Yarn, but Medibot and Kaz are here to prove you wrong by turning into a giant robot and rocket-punching the heck out of Yin-Yarn. He barely gets a shot in!
CrazyCommentaries gets one in during their Super Mario 64 Let's Play in this video, they were racing Koopa the Quick and they came to the part where they had to get past a bridge with wind blowing. Koopa looked like he pushed them off the bridge and onto the last platform, then they longjumped to the flag to eke out a victory by a mere 0.2 seconds
The milleniumfrisbee in his LP of Paper Mario manages to beat most of the game with only one badge (a HP Plus badge) and on the boss fight with the Ice King, manages to get the spell to activate when getting the star points, netting him 88 star points (beating Chuggaaconroy's record of 68 star points by 20).
In the same game, he explains a glitch[[note]]that makes the game spawn an extra seventh ball when he's rolling down the slope, a trick that is almost impossible to dodge][[/note] that makes the first battle with Robotnik very, very hard in the Game Gear installment. Some time later... he manages to jump between Robotnik and the extra ball, and from there to safety. He proceeds to freak the hell out, yelling and panting on a level on par with Chuggaaconroy's, and explain that he was never able to clear it in two separate jumps.
Chuggaaconroy, in Part 18 of his Pokemon Crystal LP— he mentions that he'd like to catch a Koffing for his team before leaving Burned Tower. Literally a moment after saying that, he encounters and captures one. What's so special, let alone awesome, about this catch? It's a shiny.
RedChocobo proving that Bullet Seed (in Emerald) and Fury Cutter (in Platinum) can be VERY helpful in the right situation.
A similar Let's Play boss kill is in Rondie Plays Fire Emblem 8, episode 021-2a. Joshua, whose mother was murdered by Callach in the last chapter, delivers revenge in the form of the One-Hit Kill Silencer. And just to rub it in, Rondie adds extra dialogue: "You bastard...you stole my Hoplon Guard, Assassin, with Shamshir, and A Support adding critical?! CURSE YOOOUUUU~"
After trying to clear a room in Hero's Cave from Oracle of Ages for about 10 minutes, these LP'ers discover one of the more entertaining ways to clear a Zelda level.
The best part? They were joking when they tried that.
TheSyndicateProject, a Youtube user who essentially does a Let's Play of Minecraft, had an awesome moment in one of his episodes, which he titled 'Luckiest Minecraft Player Ever'. Why? He went into the Nether to collect some Glowstone, with some armour enchanted with protection, pickaxes, and a few other items. During said collection of glowstone, he falls off a ledge into lava and is momentarily blinded (you can't see under lava). Upon surfacing and panicking, he slowly swims to the nearest shore, hoping his enchanted armour would keep him alive. It does, and he reaches the shore, only to have a Ghast attack him, making him run back towards his portal. He ends up being attacked by two more Ghasts, which led to him attacking one and running from the other, before diving back to safety through the portal. Upon arriving back, he is understandably freaked out, and when he checks his armour, he finds that three of the four pieces are almost broken. Luckiest Minecraft Player indeed.
KoopaTheKollector green, taking down the Boost Guardian FIRST TIME! While explaining what to do to Red, who had never played any of the Metroid games before.
An in-thread example; in Elentor's Let's Play of Final Fantasy VII, after the death of Aeris, one of the goons commented, in genuine shock, that the game actually killed off a main character. Elentor's response says it all:
Elentor: I... I did it. I... I created a FF7 thread with over 8000 replies with at least one soul not being spoiled that Aeris dies.
Artix74: Guy just straight up gives no fucks now. Endgame druids? No problem, he can just one-shot them. Similarly, fucks given by Nino? I'm pretty sure we're in the negatives by now.
In Zelda II: The Adventure of Link, the candle is a pretty important item: without it, you can't see anything in caves but yourself and the terrain. This would be problematic as the game features two fairly long gauntlets of cave scenes (Death Mountain and the Valley of Death.) So, of course, someone decided to skip it.
The Let's Play of Dangan Ronpa by orenronen on the SA Forums definitely warrants mention here, for single-handedly putting Dangan Ronpa on the map for western audiences. Now he's working alongside a different team on an English patch for the game, and a Let's Play of Super Dangan Ronpa 2 is also in the works!
The Chilean Let's Player Xoda, who beat the third chapter of Slender: The Arrival in the most difficult mode, and get caught by the Hoody thing in the elevator, as you can see in in this video retrospective, in the 4:39 minute. Of course, HE SURVIVED!
Another Chilean Let's Player, Vardoc, who beat without get killed the game Amnesia: The Dark Descent in his very fist attempt.
Tulio Ramírez, a Venezuelan Let's Player, had very troubles playing Cave Story with a damaged keyboard. He got some problems beating Misery and the Doctor in the last level, but he managed to beat the Undead Core in his first recorded attempt