MacGuffin Guardian

Our brave hero has outsmarted the guards, sneaked into the ancient and mysterious crypt and now is about to lie his hands on the object of his long quest and/or about to open the grim-looking gate leading to said object.

But wait! As he approaches, a sudden roar chills the blood in his veins and a towering, nameless creature suddenly appears to stop him. It's the Guardian!

This happens really often, with any kind of possible keeper. Monsters, Living Statues, Dragons or Demons summoned by portals and runes. It can be tracked back in old myths where a monstrous guardian keeps a treasure or a person, usually for his master. Of course, it doesn't need to be revealed in that exact way to qualify, but has just to be a monster keeping a treasure. A variation is a monster who guards not an artifact but rather the path/gate which our heroes must take.

Usually the monstrous/inhuman nature of the keeper is justified by its skills: monsters tend to be stronger and more resilient, with hard skin or maybe Combat Tentacles or enhaced senses or Breath Weapon or whatnot.

Sometimes overlap with Teleporting Keycard Squad, especially if the room appeared totally bare just a moment ago. See also Forgot to Feed the Monster when the spooky guardian is here... and already dead or incapacitated.

Don't confuse with Threshold Guardians which usually is there to test the hero, while the Mac Guffin Guardian is here to eat the hero. It may though be the test of said Threshold Guardians.

Anime & Manga

 * Jidanbo from Bleach may count, if you wish to include overgrown humans.
 * In Yaiba, Onimaru's Fortress is guarded by the Four Evil Kings, four demonic monsters acting as keepers.

Films -- Animation

 * The Cave of Wonders itself in Aladdin.

Gamebooks

 * Plenty in the Lone Wolf series, especially during the quest for the Lorestones. They often act as Final Boss for a given book.
 * Lord Haakon himself, and the monsters he summons, must be vanquished to retrieve the Book of the Magnakai at the end of book 5, Shadow on the Sand.
 * The monstruous Dakomyd guards the first Lorestone in book 6, The Kingdoms of Terror.
 * The Crocaryx and the Zadragon in book 9, The Cauldron of Fear.
 * Book 20, The Curse of Naar, can be said to be mostly a series of MacGuffin Guardians, as several Demon Lords must be beaten to retrieve each time a new Plot Coupon.

Literature

 * The Watcher in the Water from The Lord of the Rings.
 * Smaug from The Hobbit.
 * In Chronicles of the Emerged World, each elemental sanctuary has a sort of guardian. Subverted by some of them which aren't hostile at all and at least two which are guarded by a maze and enviromental hazards.
 * In the first Harry Potter book, the Philosopher's Stone is guarded by Fluffy, a huge cerberus-like beast and by a Troll.
 * Beowulf has the giant dragon guarding his hoard of gold inside a barrow.
 * Too many to count in Conan the Barbarian including the Thing in the Crypt, several Giant Snakes and at least one Giant Spider.
 * Fablehaven has the cat-thing guarding one of the artifacts which has nine progressively more dangerous forms.
 * In the first Gotrek and Felix book, there's a huge, Warpstone-mutated Troll guarding the treasure inside an abandoned dwarven tomb.

Myths & Religion

 * Cerberus may be the Ur Example along with many other monsters like Ladon, Argo and Eruption.
 * The Golden Fleece was guarded by a gigantic Dragon.
 * Norse Mythology: Garm, the bloody hound of Hell.
 * In Japanese Mythology there are Gozu and Mezu, the hell keepers.
 * In The Epic of Gilgamesh there's a fire-breathing giant Kumbawa who guards a forest of precious trees. Unlike other examples however, Gilgamesh's objective is the guardian himself, as he wishes to kill him for fame.

Tabletop Games

 * Stormbringer supplement Demon Magic, adventure "The Velvet Circle''. The box the adventurers are seeking is guarded by a demon named Tyik Tyva. Inside the box is a Melnibonean Wheel worth 500,000 large bronze pieces.

Video Games

 * Spoofed to no end in Battle for Wesnoth where the presence of a Giant Squid in a pool just outside the entrance of the Dwarven Kingdom is lampshaded. In a particular campaign said gag was brought Up to Eleven.
 * Used more seriously in The Hammer of Thursagan where the tome needed to open the secrets gates in the final level is guarded by several vicious huge spiders.
 * The Guardians of Temen-Ni Gru in Devil May Cry 3 may count. Most of them at least.
 * In Final Fantasy II, each MacGuffin necessary for the plot advancement was guarded by a fearsome monster, including the Sergeant, Adamantoise and Shrieker.
 * Grand Jewel, Polter Armor and The Last Kraken from The Legend of Dragoon.
 * Onimusha has the huge hound Gertrude in the third game. The sequel features the gigantic, bug-looking keeper of Sawayama.
 * Tobi from Okami. Unlike other examples, however, he must be defeated in a race.
 * The second Rayman game has its share, including the Guardian of the Cavern of Bad Dreams.
 * The huge Kraken in Tomb Raider : Underworld was probably left behind as a guardian.
 * MARDEK: Chapter 3 features guardians in each of the elemental temples you visit. Fire had a wise, flaming dragonlike guardian named Girru who tests you by combat and finds you worthy, Water had a giant lobster-seahorse thing with a human rider, and Earth had the Rock Mole. Darkness was guarded by a wolflike alien mage called Solaar, but she had already been taken out by a villain when you get there and in fact joins your party in hopes of catching the thief.
 * In God of War, Kratos must fight several Guardians during the course of the three games, including Pandora's Guardian, the Mole Cerberus and Skorpio.
 * In EarthBound, each of the Sanctuaries is guarded by some sort of monster.
 * The Barrier Trio would count too, from the sequel.

Web Comics

 * Order of the Stick
 * The outdated monsters guarding Dorukan's Talisman. Justified, since it's the Talisman itself which lured them there.
 * The Black Dragon guarding the Starmetal fragment in the Wooden Forest.
 * Kraagor's Gate is said to be protected by a bunch of monsters.

Western Animation

 * The SpongeBob SquarePants episode, "The Lost Mattress" had Mr. Krabs' prized money-filled mattress guarded by a ferocious worm at the junkyard, after it got thrown away.
 * Played for laughs in one Simpsons episode where the secret exit from the Nuclear Power Plant is guarded by a Giant Spider with a taste for human flesh.
 * Wakfu has Grougaloragan's Dofus guarded by a giant Stone Golem, able to switch its head (and power) for another if beheaded.