Self-Guarding Phlebotinum

For some reason or another, you can't get to the McGuffin because it produces a forcefield or has a forcefield surrounding it. Possibly due to it being a Loyal Phlebotinum or Empathic Weapon. Maybe there is an enchantment upon it that causes it to repel a certain type of being, such as demons, or maybe it's a curse that will let you touch the object but causes adverse side effects, such as death.

Anime and Manga

 * In Inuyasha, the sword Tessaiga has a barrier around it that prevents demons from touching it. Humans and half-demons can touch it without pain, however.

Literature

 * Harry Potter and the Half-Blood Prince: The cursed opal necklace that kills anyone who touches it. Bonus points for being a Chekhov's Gun from its brief mention in Chamber of Secrets.
 * The eponymous Silmarils from The Silmarillion burned any evil creature touching them, such as Morgoth and Carcharoth, while sparing the good-aligned heroes such as Beren and Earendil. Becomes a plot point late in the book, when two remaining sons of Feanor (Simarils' creator) finally get their hands on their "heirloom"—only to find that the Simarils reject and burn them, after all they have done to get them back.

Film

 * The Wizard of Oz. When the Wicked Witch of the West tries to take the Ruby Slippers from Dorothy's feet, they generate an electric shock field that prevents their removal.
 * Colossus: The Forbin Project: The titular Master Computer's main defense is that it was built inside its own radiation-spewing nuclear reactor.

Live-Action TV

 * The Charmed Ones' Book of Shadows won't let you touch it if you happen to be evil.
 * There were also various amulets and charms which protected against evil including crystals that when placed in a circle formed a cage of energy that one couldn't cross, whether to get in or out.
 * Also once when Piper pulled Excalibur from the stone, the sword would let no one else but her touch it, though a demon used a spell to amass a bunch of power and take it from her.
 * In season 7 Pandora's Box protects itself by teleporting to its next guardian when its current protector dies.
 * The Grimoire, the Evil Counterpart to the Halliwell's Book of Shadows, would not let any good being come in contact with it.

Tabletop Games

 * Dungeons & Dragons adventure C2 "The Ghost Tower of Inverness". The Soul Gem is surrounded by an invisible force sphere which must be broken by the PCs if they want to retrieve it.

Western Animation

 * In the Star Trek: The Animated Series episode "The Jihad", the Soul of the Skorr is protected by a force field.
 * Adventure Time: In "City of Thieves," the King of Thieves' tower has a barrier around it that repels all thieves.
 * The Omnitrix from Ben 10 generates a small field around itself when someone who is not the person who it is currently attached to tries to touch it. However, it should noted that the Omnitrix is neither Empathic nor Loyal and only tries to protect itself; in fact, one way you can obtain it is to kill the current user and then take it for yourself.