Near the beginning of Ninja Scroll, Jubei confronts Tessai, a bad guy with the ability to harden his body like stone. Jubei casually mentions that he can't be invulnerable everywhere, right before throwing a needle into his eye.
The manga adaptation of Kingdom Hearts 1, in a break from the game's events has Sora use a quote from Battle of the Bengal Tiger (When you encounter a giant enemy, aim for the eye. No one can train one's eyes...) against the giant Heartless.
Mazinger Z: Gumbina M5 armor was completely impervious to Mazinger-Z's weapons. Kouji not even was capable to scratch it or dent it. Its weak point were its large eyes located on the chest. Sayaka ended up the battle when Aphrodite-A's Torpedo Tits managed to hit them. Ouch.
In the "Mazinger-Z vs Great General of Darkness", Kouji was sword-dueling against a clearly superior Warbeast had pinned Mazinger-Z on the ground and was trying run its sword through it. Kouji shot Mazinger's drill missiles and managed hit one of its eyes. The Warbeast crumbled down due to the missiles boring into its head and exploding. Double ouch.
Ozones B3 subverted the trope. It had a huge, glowing, single eye on its head... but it was not its weak point, and Kouji did not try to destroy it.
Partially subverted in the first chapter of Shanghai Youma Kikai, where Jack uses his last bullet to shoot the demon in the eye. The demon tells him that even that won't work. Turns out Jack's real intention was to create a blind spot do some other really cool stuff which I shan't mention here.
In a particularly badass moment from the Eclipse from Berserk, Guts uses the broken-off horn of a demon this way to devastating effect on several of the horde of monsters trying to eat him alive.
This is one of the better ways that the title cyborg girls from Gunslinger Girl can be killed due to their extensive cybernetic enhancement. And they know it too. One committed suicide this way, another used it in her mercy death.
In Yaiba, Silver's body is rubber-like everywhere, but his eye do bleed and is his weak spot. His brother Gold, however, avert this by having a rubbery eye too.
In the second episode of Mirai Nikki, Yukiteru uses one of his signature darts to stab and completely ruin Minene's eye. Fortunately she gets a badass eyepatch from this event and all is well. (She almost blocked the dart with her phone, but seeing as if the phone is damaged she will be killed, it was a smart move to drop her guard.)
Early in ½ Prince, the main character's party runs into a giant high-level monster with very tough skin. They eventually realize that the eyes aren't protected, just very difficult to hit with melee weapons.
Bleach: Kenpachi Zaraki lampshades this trope during his fight with Nnoitra Gilga. The trope itself, however, ends up being subverted. Kenpachi fails to cut Nnoitra's eye (his blade passes harmlessly through Nnoitra's hollow hole which is hidden behind his Eyepatch of Power). Also, in the end, Kenpachi manages to get through Nnoitra's Hierro by other means.
"I've had several encounters with guys who wouldn't shut up about how my sword couldn't cut them. But... I have yet to meet someone whose throat or eye I couldn't cut!!!"
This is pretty much the only way to hurt the Thing.
In Ghost Rider, the All-New Orb (whose entire head is a giant eyeball) is taken out by a trap that flung a board with a nail in it into his eye. He survived, but was temporarily blinded and gravely hurt.
In ElfQuest, this was the way they killed Madcoil.
In one crossover, Silver Sable stopped Luke Cage: Hero for Hire by knocking him to the ground and aiming a gun at his eye, saying that she was willing to bet that his eye wasn't as bulletproof as the rest of him.
While the Star Wars prequels have felt a LOT like video games, a certain scene in the opening of Revenge of the Sith had Obi-Wan channeling Peppy Hare. And they played it straight!
The Specials: "Tell your brother the next time he wife-beats her, hit her in the eye. Her eyes are normal."
Parodied in Galaxy Quest. "Go for the eyes!" "It doesn't have any eyes!" "Then the nose, the throat, its vulnerable spots!" "It's rock, it doesn't have any vulnerable spots!"
Kill Bill: This is how The Bride defeated Elle Driver, who had bad luck when it came to this trope.
In Demon Knight this is one of the only ways to kill a demon, the other being to use the blood in the Key. This only works on weaker demons though — the Collector is only mildly annoyed after Jeryline stabs him in the eye. Splashing the special blood into his eyes does the trick.
What the human snipers does exactly against several Decepticons in Transformers: Dark of the Moon during the climatic battle in Chicago, allowing NEST to take down a couple of them without Autobot aid.
It's not just the Decepticon mooks that fall victim to this. Starscream is killed by having his eyes taken out and a grenade dropped inside his head through one of his now-empty eyesockets.
Pacific Rim. After two Jaegers are destroyed and a third immobilised, the two surviving pilots climb out onto its hull and take potshots at the kaiju's eyes with flare guns because it's the only weapon they've got left. The creature has six eyes though, and getting hit in one only pisses it off.
While not a fatal move in itself, Harry is greatly aided at the end of the second book, The Chamber of Secrets, when the basilisk he is facing gets its eyes plucked out, rendering it unable to use its One-Hit Kill (and even still petrifying when reflected) gaze.
Ender's Game: How Ender finally gets past the Giant's Drink in the fantasy game.
In A Horse and his Boy, the Hermit (remotely watching a battle) observes that one of the Narnian Giants is down, "shot through the eye, I suppose."
The Colour of Magic: Did this to Bel-Shamharoth just before it could devour Rincewind, the camera that Rincewind was holding flashed into its giant eye causing enough pain for it to retreat to the chthonic planes.
Brought up by a Klingon hunter in one Star Trek novel: while hunting a particularly large and aggressive beast as part of a contest with a just-discovered warrior race, he muses on how it's good sense to aim for the eye. Best-case scenario, your shot goes straight into its brain. If you hit, then you've at least partially blinded it, giving yourself an advantage.
Similar to the Real Life spitting cobra example below, Pip of Alan Dean Foster's Pip and Flinx novels prefers to aim at the eyes for her one-hit kill venom.
Lampshaded and averted in Codex Alera, where it's noted that if the Vord hulk's had eyes attacking them would be a good way to take them down.
In The War of the Flowers the preferred goblin method of killing dragons is to shoot them in the eyes with poisoned arrows.
The only way to reliably take down a Mūmakil in the Lord of the Rings was to aim for their eyes. The skin of the great elephant ancestor was thick and extremely tough, deflecting arrows and blunting swords.
This is how Kaladin managed to kill a Shardbearer in The Stormlight Archive, he rammed a spearpoint through the visor slit in his armour.
The only exposed point on the monster Wyrm in The Book of the Dun Cow is his enormous eye. Mundo Cani manages to defeat him by jumping onto this eye and slashing at it with a cow's horn until Wyrm is blinded.
This could be applied somewhat to Xander as well. Sure he's had an arm broken here and there, and has been beaten with a Troll God's Hammer, but all to little actual effect. It was only an attack on his eye that really harmed him.
Right after telling his fighters to "go for the (...) eyes. Everything's got eyes." Ouch.
In Brimstone, the eyes of the fugitives from Hell are their only weak spot (because eyes are the windows to the soul), thus Zeke has to shoot their eyes to send them back. Interestingly enough, he's also immune to everything except the eyes.
As the Devil points out, that's because Zeke is also a damned soul himself.
In Doctor Who, the Daleks' eyepiece is the most susceptible to gunfire, though only comparatively.
On more than one occasion, Daleks have been incapacitated by damaging or covering their single eyestalk: "My vision is impaired!! I can not see!!"
Notably avoided on one occasion.  "MY-VISION-IS-NOT-IMPAIRED!"
The show parodied this once in Remembrance of the Daleks. After the Doctor repeatedly tells soldiers to shoot the Daleks in the eyepiece throughout the story, Ace ends up blowing one up entirely with a rocket launcher.
Despite being primarily a video game trope nowadays, this is actually Older Than Feudalism. How does Odysseus defeat the Cyclops Polyphemos? By shoving a burning stick in his eye.
A very common heel tactic is to rake or poke his opponent in the eyes.
In his commentary, Jesse Ventura regularly pointed out that no matter how tough someone is, a finger to eye will stop anybody.
In Warhammer 40K, the Tyrant Guard species of Tyranid lack eyes completely, in order to avoid this trope.
Minsc from Baldur's Gate has this in one of his attack quotes- he orders his pet miniature giant space hamster to, well....
"Go for the eyes, Boo! GO FOR THE EYES! EYYAAAAAAAAAAAAHHHHH!!!!!!!"
The final battle of Shadows of Amn features the memorable line "Boo will finish his eyeballs so he will not rise again!"
If anyone has read The War Of The Spider Queen series, set in the Forgotten Realms, the 'finish his eyeballs' quote feels remarkably similar to a certain situation where a character has his eyes EATEN by a rat to put NEW ones in...
And the Citadel expansion for Mass Effect 3 has a scene where the Big Bad tries to dispose of Shepard's hamster. S/he gives it this advice if anyone else tries to mess with it.
The Legend of Zelda games use this trope often. Most of the examples are different iterations of Gohma.
This is so common in the series that they incorporated it into puzzles, starting in The Legend of Zelda: A Link to the Past, in which a statue of a cyclopean monster acts as a switch when shot in the eye. In the first 3-D games, an ornate eye on the wall would act similarly.
The devs even have some fun with this. The boss of the Temple of Time is Armogohma, a giant spider with an eye on its back, which also serves as a weak point and a weapon. Hilariously, the eye is revealed to be a smaller spider that was controlling the bigger spider! Even Link has a stunned look on his face.
It's not just the Phantoms. Bellum himself has many, many eyes in octopus form which you must attack; when he possesses Linebeck and becomes a superpowered version of the Phantoms, and, like the Phantoms, has an eye on his back (albeit a much bigger one).
Most of Bellum's monsters have the same eye as Bellum. For the big blue cyclops monster, you can't go near them at all unless you fire an arrow in its eye first, thus stunning it.
The Misery Mire boss Vitreous from A Link to the Past is nothing but a giant eye, surrounded by innumerable smaller ones. What else are you going to hit?
Let's not forget the numerous eye switches found throughout the games, which usually have to be hit with an arrow or slingshot.
The Gohma in The Legend of Zelda: The Wind Waker has an eye as its weak point, but it also has an armored lid that comes down every time you try to hit it at least, until you drop a huge rock on its head enough times to break its armor.
Rocktites and the Ocean Temple boss Phytops in Spirit Tracks
Basically, if it's got a big eye, you're probably supposed to shoot at it.
Phantoon from Super Metroid can only be damaged when his eye is open as well.
The second type of boss in Metroid Prime: Hunters, which are almost nothing but huge, floating eyes.
Really, both of the recurring bosses require you to shoot some eye-like structure. The Slench is more annoying because you have to go for not just the eye, but the pupil, and it's aggravatingly agile.
In Fusion, some doors are blocked by giant eyes. Absorbing their Core-X restores a large heap of energy, so they are actually there to help the player (the next room usually contains a boss). These doors are similar to ones found before bosses in Super Metroid, and in both cases the doors are capable of shooting Eye Beams.
Metroid Zero Mission has Mother Brain sporting both Eye Beams and the eye weakness.
The end boss Gene Worm from the Half-Life expansion Opposing Force had this. The boss itself is invulnerable but hitting the eyes makes the boss' belly open and briefly reveal the only vulnerable area, accompanied by the boss teleporting in a Mook to keep the attacker occupied while regenerating its eyes. While blind, the boss is unable to attack but blindly thrashes around.
The earlier Pit Worm Puzzle Boss had this trope as well; while not actually inflicting any damage, shooting it in the eye causes the worm to shriek in pain and protectively cover the eye for a moment, making it unable to use its Eye Beam for a short while.
The Yellow Devil and its different incarnations in the Mega Man series.
In both Star Fox and 64, you must shoot Andross's eyes in order to reveal his brain or the robot duplicate on Star Fox 64's Easy route. In 64 you first had to destroy Andross's hands, but shooting the eyes would stun him momentarily, making that far easier.
Additionally, the Bacoon from Star Fox 64 is a giant one-eyed clam, prompting Peppy to call out this trope verbatim.
The person that made this page before the wipe can confirm that this is the Trope Namer, actually.
Not surprising. Peppy's advice had a tendency to be memorable.
A variation is played in Super Mario 64: one of the enemies is simply a huge eye, and you defeat it by running around in circles.
One of the mini games in Mario Party does this exactly the same as well.
It's also played straight with the boss of Shifting Sand Land, two giant stone hands with eyes in the palms. Whacking 'em in the eye causes damage, but only when the eye is open.
Mario Kart DS has the same hands as one of the bosses in mission mode and just like in Super Mario 64, you can't damage the eyes unless they're open.
In Fallout 1 and Fallout 2 (but not 3), it's possible to aim specifically for the eyes of your opponent (or appropriate sensory organ). It's usually the most difficult shot to connect with, but landing a critical hit to the eyes will almost always kill or blind a creature, making it mostly harmless or dead.
In Fallout 1, Harold mentions that a Deathclaw's eyes might be its weakness. It's true. Using this knowledge you can actually go kill one at a low level. However, since it's still so tough you need to hit it dozens of times even so, this leads to perhaps the most ridiculous Death of a Thousand Cuts ever.
Deathclaws have incredibly sharp senses of smell and hearing, but rather weak eyesight. So blinding them is only a minor annoyance, but it's still the softest part of their surface and has a possibility of piercing to the brain. Damaging them anywhere else generally requires anti-tank weaponry.
A character in Fallout: New Vegas claims to have done the impossible and shot a Brotherhood of Steel Paladin through the eye hole of their Power Armor. If you've met the Brotherhood and gotten in their good books you can challenge these Blatant Lies by pointing out that their eye protection is bullet proof. He also claims to have killed a Deathclaw (misidentified as "Deathjaw") this way, earning him the nickname "Dead Eye". As with 3, however, it's not actually possible to target the eyes.
Or if your gun skill is high enough, point out there is no such thing as a 11mm pistol
The final boss from Resident Evil 4 is an extremely odd creature with eyes on its articulated limbs. While you do have to shoot it to keep the fight moving, you kill it with the staple Resident Evil anti-boss weapon: a rocket launcher.
Not to mention the fact that if you do shoot the eyes on the limbs, it gives you the opportunity to shove your ubiquitous knife into its main eye. Repeatedly.
Eligor from Order of Ecclesia. Easier said than done as Eligor is a gargantuan stone centaur armed with a massive sword, mounted crossbows, harpoon tail and powerful kicks and his eyeball is located on the back of his head.
In Sonicand the Secret Rings, one of the bosses is an enormous, purple scorpion with four eyes (two on its tails, one on its back, and another in its mouth). Of course, Sonic must use the Homing Attack on the scorpion's eyes to defeat it.
Previously, there were the Black Bull and Devil Doom in Shadow the Hedgehog, with the unskippable obvious hint "The eye is its weak spot" in both fights. Thanks, Einstein.
Notably subverted in Shadow of the Colossus. While the entire game is made up of boss battles against giant creatures, most of whom have glowing eyes, they are almost never a weak point. Even when facing the one where you actually are supposed to aim for the eye, it's only a preliminary attack and not what actually kills him.
The stage 6 boss of the GBA game Gradius Galaxies/Generation is simply a giant eyeball. Naturally, the off-screen announcer that usually tells you to "Destroy the core!" when a boss shows up will instead tell you to "Shoot it in the eye!"
The first boss in Light Crusader consists of a meteor with a ton of craters and an eye that pops up in random craters. Aiming for the eye is the tactic to defeat him.
Devil May Cry 3 has the boss Beowulf. While it's not compulsory to hit him in the eye to damage him, and he does have a light-blast to- try and deter your doing so, striking him in the eye does more damage and causes him to flail about for a bit, allowing one to get a bit more distance from him. More importantly however, striking him in the eye for the hit that causes his Turns Red response will cause him to fall to the ground briefly, allowing for some more hits to be delivered against him. You will need those hits.
Completed Reapers in Mass Effect 3 are mostly impervious to weapons under dreadnought-grade, except for the firing chamber of their Fricking Laser Beams, which sits in the center of each Reaper's "face" and happens to resemble a single giant, baleful red HAL eye. Of course, the Reapers aren't totally stupid, so they cover this weak point with thick armor plates when not firing, meaning anyone hoping to get a lucky shot off will generally have to do it while dodging laser beams that can cut through warships with ease.
In Pac-Man World, King Galaxian has four eyes. You defeat it by destroying its eyes, but it becomes faster, uses more shots, and summons more difficult enemies after each eye is destroyed.
In World of Warcraft, one of the final bosses of the old world was the EYE of Eldrich Abombination Cthun. Merely defeating Cthun's eye was for a long time considered more difficult and hardcore than any of the raids that followed it.
In Gauntlet: Dark Legacy, if you found the Javelin of Blinding, your character would throw it into the Plague Fiend's eye, temporarily reducing his near-perfect accuracy.
Oddly enough, the Whomping Willow in the Harry Potter and the Chamber of Secrets game.
The second form of the final boss in Purple can only be hurt by throwing a frisbee on his pair of enormous eyes.
Ghostbusters 2009 does this at least twice. The first time is with the Collector (and it's a VERY SMALL eye), and the second is the Juvenile Slor. The JS is a double example, as you must slime the single eyeball on its head and contend with the four orbiting "eyes" which threaten you and the others. Naturally there are about a hundred eye-puns throughout.
The Sega Genesis game does this a few times, too. There's a One-Hundred-Eye Centipede, which is nothing but eyes, and a floating egg with an eye/mouth (!) that can shoot lasers.
In BorderLands headshots result in large amounts of critical damage. For enemies that have armored heads you need to aim for the eyes.
This is how you have to defeat the Eyebot in Heavy Weapon, by attacking the eye when it is open.
In La-Mulana, Viy is only vulnerable when the lid of his eye opens, which is also when he can unleash his most powerful attack.
Overlapping with Eye Scream, one of the finishing moves against dragons in The Elder Scrolls V: Skyrim is for the Dovahkiin to jump onto the dragon's head and stab or slash it in the eye.
Lampshaded in Schlock Mercenary, when a human sniper hits the massively exposed eyeball of Ebbirnoth, member of a cyclopean species called Unioc. Bizarre Alien Biology proves him wrong, as the Unioc eyeball is just an eye, and although the attack blinds Ebbirnoth (and probably hurts a lot), it has less effect on him than an attack in a similar location would have done to a human (Unioc brains are located in their pelvis).
Later played straight when the sniper tries to shoot Schlock, whose eyes really are his only vulnerable point.
Referenced in Faulty Logic. When asked for advice on a Zelda boss, Jalyss recommends shooting it in the eye without bothering to look. She then provides a surprisingly reasonable-sounding explanation of why (apart from the obvious) Zelda bosses work that way.
Cardholder: I bet his eyes are as gooey as the next guy's.
While it may just decide to bite its attacker with venomous fangs, the spitting cobra will usually target a spot where its projectile venom will be easily absorbed (and thus disable the opponent). Guess where that spot is.
The eye is usually a good weak point in real life. It's soft, easily damaged, very painful, and causes a loss of vision. It's one of the first places you're taught to aim for in a self defense class.
And on a similar note, "When someone stares at you, don't be intimidated. Eyeballs are soft, sensitive and filled with goo. They cannot hurt you."
This trope is sufficiently widespread in nature that many species of insects, and a few small vertebrates, have evolved markings that resemble false "eyes." These markings are a decoy for predators, ensuring they'll direct their attacks towards the marked animal's tail or other less-essential body part, rather than its actual eyes.
It also doubles in usefulness as it's intimidating as hell.
In medieval plate armor the eye slit of the helmet was a very vulnerable spot. If it was too small the fighter would be almost blind. If it was too big, an arrow or crossbow bolt could pass through it and kill the fighter. During a battle a knight might lift his visor to get a better look at what was happening around him only to get shot right in the eye.
"Lucky" lance hits to the head during cavalry charges or jousting tournaments could also go through the visor and the eye at times; the results were not pretty. Just ask king Henry II of France.
The usual method for dealing with a mounted knight in the Middle Ages: A) stop the horse and pull him off B) dogpile him C) slot a dagger through the eyeholes.
Remains symbolically true of armored vehicles: any sort of viewing slit provides a gap in the armor, whereas a camera or other remote system is itself vulnerable to being shot off.
Several surfers and swimmers attacked by sharks have managed to get away after landing a lucky punch in their eye.
In fiction, trained hawks and falcons are often shown perching on their owner's shoulder. In Real Life, one of the first things a budding falconer is taught is, keep the bird away from your face unless you really like eye-patches.