Nunnally from Code Geass gets a role as a living MacGuffin. This is partially because she's the protagonist's little sister, partially because she's so sweet and seemingly helpless that most characters want to protect her, and partially because she's a princess.
C.C. also gets used as a living MacGuffin, as evidenced by the existence of a special canister designed to contain her. In Code Geass R2, she has this role because she has a special power that is needed in order for The Emperor's master plan to work.
Lelouch in early R2 also qualifies, before he gets his memories back.
While it's debatable whether the torches in Shakugan no Shana are "alive", Yuuji Sakai is generally treated as living by the main characters. That's partially because unlike other torches, he isn't going to just go out one day. But it's also because he's managed to validate his humanity, even before he found out he wasn't going to become Ret Gone.
Insane Casca during the Retribution arc in Berserk. Not only does Guts, who has a right to her being her protector, want her, but everybody is taking Casca in this arc, primarily the pagans who want to make her their queen and the Holy See who want to burn her at the stake.
Witch Hunter: The Hero, Tasha Godspell, is revealed to be both the key to the Big Bad's plans for wiping out humanity, but also the key to stopping these plans and saving mankind. Exactly how this works has yet to be explained. There are also several other witches out to capture him, including his own sister.
Naruto. Sasuke becomes this after he leaves the Leaf Village. Jinchurikis provide a straighter example.
The first half of Last Exile concerns Claus and Lavie (and later, the entire crew of the Silvana) trying to keep Alvis out of the clutches of the Guild. Why they're hunting her isn't revealed until the last episode. Turns out she's a living "ignition key" for the eponymous space ship.
In an early episode of Pokémon, Ash's pikachu catches the attention of three shady individuals. Queue many years of Jessie, James, and Meowth attempting to capture said pikachu.
Eren is hunted by everybody so that he either gets to be humanity's greatest weapon, dissected, executed, or be brought back to fellow Titans. It's later revealed that he is also able to control titans to an extent. This is why people with powers the same as, or even stronger than his were willing to go to such lengths to capture him alive. Christa also becomes an example later on, due to her heritage and ability to reveal the secrets of the Walls being revealed. The Survey Corps' solution to this is to sweep both of them under the rug until they reach adulthood, upon which they can deal with it better.
The Beast Titan, the only non-Shifter Titan thus far shown to be fully sentient, is stated to be this to the Titan Shifters.
Crime Zone starts off with Aburaya Shiro, the main character who thought that he was just an Ordinary High-School Student finding out that he is somehow key to the plans of the vampires who've been put on the run by humankind, and that the government haas been keeping a close watch on him for years as a result.
Banagher Links of Mobile Suit Gundam Unicorn qualifies as well. Thanks to a dying requestfrom his father, he eventually becomes the sole pilot of the titular Gundam, itself being the key to Laplace's Box. Thus he becomes a primary target for various factions who are all after the said box.
In Fairy Tail, the Black Mage Zeref is treated this way even centuries after his supposed demise. Several villains are out for his power, if not his very existence. At least one cult is shown that worships him and wants to revive him, one Dark Guild devoted all of its efforts to unsealing him, and another Dark Guild composed of demons he created venerates him and is doing everything in its power to honor his wishes despite never having met him. Zeref himself regards their efforts with either contempt or mild amusement, and otherwise doesn't really care about them that much.
Yorick in Y: The Last Man is a male example; various factions want him, mostly alive, some dead.
Ramona Flowers in the Scott Pilgrim books (YMMV, of course): the protagonist must go through several obstacles to be with her, but we are shown very little about the relationship, or even Ramona Flowers herself, except that we are assured of her awesomeness.
Jot Soora and Monima Das in Assassin's Creed: Brahman, with both the Assassins and Templars hunting for them so they can access their genetic memory and discover the location of the real Koh-i-Noor diamond.
In the pre-Disney versions of those fairy tales, the nameless prince was the Living MacGuffin; for example, Cinderella competed with her wicked stepsisters for the hand of the prince, who is treated as a non-entity who exists in the story only to provide the winner with a castle, title, and wealth.
Troy is a subversion. It is established early on that Agamemnon is only using Helen as an excuse to wage war on the city. At one point Helen says she would give herself up to prevent further violence, but Hector makes it clear that even if she did, it would not end anything. Agamemnon even says that he didn't come here for Helen, but for Troy.
In The Darjeeling Limited, the brothers use a trip to find their long left mother to tell her about their father's death and try to bond with each other.
Another long lost mother variation of the living MacGuffin is Mike's mother in My Own Private Idaho, whom he never finds.
Doug from The Hangover, who is given all the characterization of a very Nice Guy to both his friends and brother in law. So much so that you can honestly believe these guys would shake down all of Las Vegas to find him.
In Kill Bill, finding Bill so she could kill him is the entire focus of the Bride's Roaring Rampage of Revenge... well, that and revenging herself on the people who could lead her to him.
Zuzu Petals in The Adventures of Ford Fairlane. Everyone Ford meets in the first act tells him to find her, and that's his motivation until he does, at which point it becomes clear she's not even involved in what's going on. After that she's more of an Escort Mission, albeit one attended begrudgingly.
Ford: Don't worry. If you fall, I'll make it.
Kee in Children of Men. She's the first woman to get pregnant in almost 20 years. The main characters have to try to keep her (and the baby) alive and out of the wrong hands.
Apocalypse Now is centered entirely around Willard's mission to travel to the compound of an insane colonel and to kill him. He becomes even more determined to find and confront the colonel as he learns more about him from previous military reports.
The 2007 film version of Sweeney Todd portrayed Johanna Barker as this, especially as they cut most of her songs and speaking parts from the original musical.
The plot of the film Poetic Justice has four friends go on a road-trip from Los Angeles to Oakland, California to visit Lucky's cousin, Kalil. They find out he's been shot and killed once they arrive.
Roxanne from A Goofy Movie is the reason Max is traveling. He wants to show off to her at a place opposed to his father's destination.
Elysium: Max becomes one when all the security coding for Elysium gets uploaded into his brain, coding that would basically let the user do anything they want. Spider and co. want the information to disable the Elysium security systems and make everyone on Earth register as a citizen, Delacourt wants it to overthrow Elysium's current leadership, and Kruger wants it to take over Elysium and do... unpleasant things.
In X-Men: Days of Future Past, Mystique is the lynchpin to the Bad Future in more ways than one. Her murder of Trask not only drives others to complete his work, but her subsequent capture provides them with the key to making Sentinels unstoppable, which is why Erik tries to kill her before she can kill Trask.
Queen Guinevere is also not in distress, as most versions have her go willingly with Lancelot. The whole kingdom goes down because the vassals have to choose sides, help Arthur get her back, or help Lancelot keep her.
Most of the variations have the vassals torn between personal loyalty to Arthur (who would pardon his beloved and his best friend, despite the pain they have caused him) and loyalty to the law itself which demands she and Lancelot be tried for treason against their king (with the lawful side being spear-headed/manipulated by one enemy or another of Arthur's).
Jeeves himself is highly sought-after; Bertie notes that plenty of his friends want to steal him and make him their valet, and this is borne out in Thank You, Jeeves when Jeeves quits and Bertie's pal Chuffy snatches him up almost instantly. Later in the book, Jeeves goes to work for American multimillionaire J. Washburn Stoker, who offers him a position, before returning to Chuffy and finally settling down with Bertie again.
A few crop up during the course of the Prydain Chronicles — Hen Wen the pig in The Book of Three, Princess Eilonwy in The Castle of Llyr, and Taran's long-lost parents in Taran Wanderer.
In Tobias Buckell's Crystal Rain, Oaxyctl is looking for John deBrun because he wants to torture "the code" to a spaceship out of him. We later find out that John is the code — he has to be bodily present (and alive) to open the spaceship.
It could be argued that The White Rabbit is one. The entire reason Alice ends up in Wonderland is her curiosity about the Rabbit. And it's often the Rabbit, constantly hurrying from one place to the next, which brings her from scene to scene.
Bree Pym is this for Lori and Bill's college chum Cameron; they spend most of the novel Aunt Dimity Down Under pursuing the girl over New Zealand's North and South Islands to deliver the Pym sisters' letter and convince her to meet Ruth and Louise before they die.
Deconstructed in the Sword of Truth: while fully half of the main cast are some level of this trope, the Confessors have it notably bad. Confessors can't control their ability during moments of passion (read: sex), so they can't have kids with someone they like, or they'll destroy their mind. Male confessors are such a threat that all male children of Confessors have to be strangled at birth, and for their troubles, the Confessors are feared and hated, and since they're raised secluded, have almost no friends. By the time Kahlan met Richard, all of her few friends had been murdered by D'Haran assassination teams. Yeesh.
Wizards are able to create these in general; the Rahl bloodline is the result of such an experiment, as are Slides, Dreamwalkers, Mriswith, the Sliph, and a whole host of other exciting pieces of work.
The Dresden Files has the Archive, a repository of all written works from all of human history. Because knowledge is very literally power in the Dresdenverse, she's a terrifyingly powerful wizard when called upon. While most wizards see her only as the Archive, Harry calls her 'Ivy'. Names have power in the Dresdenverse, so calling her that actually makes her more human and less scary-supercharged-twelve-year-old.
In Judith and Garfield Reeves-Stevens's novel Star Trek: Federation, Zefram Cochrane, the inventor of the warp drive, is one in the TOS and TNG storylines. Former fascist leader Adrik Thorsen is obsessed with revenge against Cochrane, and Kirk wants to protect him. Picard was mostly an innocent bystander dragged into it by Thorsen.
A Song of Ice and Fire has Davos Seaworth going to Skagos to retrieve Rickon Stark, as he is a key on getting the Northern Houses to fully side with Stannis, as the North are fiercely loyal to the Starks and they hate Boltons for their part in the Red Wedding.
Towards the end of Maddigan's Quest, it's revealed that Jewel, not the talisman, is what gives Eden his powers.
Farscape: Poor John Crichton. By the end of the series, half the Galaxy which he's close to blowing up with his knowledge of Wormholes is after him. He's close to a Ginger Snaps moment.
Mr. Big in Sex and the City, to the point that they don't even bother to give him a real name. You find yourself wondering what is wrong with Carrie Bradshaw and then you remember ... oh yeah, she's Carrie Bradshaw.note They do in fact reveal his name in the movie
Stargate Atlantis: Teyla's baby is a MacGuffin for Michael as he wants to use the newborn's DNA to advance his hybrid research. Since Teyla's an Action Mom, he doesn't get very far.
Kamen Rider shows have a few cases of Living MacGuffins, most of which are people the bad guys are after. Their nature is revealed towards the endgame, so be warned of spoilers.
Kamen Rider Den-O has Hana, who is revealed to be the Junction Point, a special type of Singularity Point whose destruction will ensure the existence of the Imagin.
Kamen Rider Double has Phillip, who's Dead All Along and was responsible for the creation of the Gaia Memories due to his connection to the Earth as he was brought back as a Data Being after dying. As an interesting variant, the bad guys already had Phillip in the beginning, though he was rescued by Shotaro and his mentor.
Kamen Rider Fourze has Kengo, who's actually a being created from an alien artifact that is sought after by the Zodiarts.
Kamen Rider Wizard has Koyomi, who's you guessed it, Dead All Along, though she's temporarily brought back to life through a ritual that kickstarted the series. She only becomes important in the endgame as not only is her time running out, prompting her father to step up his game, but also because another Phantom wants the thing that keeps her alive: the Philosopher's Stone.
Here's a negative version of the Living MacGuffin: Sephiroth during the first half of Final Fantasy VII. Both Cloud's party and Shin-Ra are hell-bent on finding the guy, and he acts as the game's main antagonist to boot.
At the beginning of Yoshi's Island, Kamek kidnaps Baby Luigi (who becomes the Distressed Dude), but the stork forces Kamek to drop Baby Mario, who falls onto Yoshi. Baby Mario becomes a free MacGuffin, whose only role is to point the way to Baby Luigi, while the Yoshis perform the MacGuffin Escort Mission that will reunite the babies and rescue Baby Luigi.
Then in Yoshi's Island DS, Kamek and the Toadies kidnap Baby Luigi again, and several more babies. The Big Bad (adult Bowser from the future) is searching for the seven star children.note Seven stars had fallen and were resting inside the hearts of certain babies. These babies are said to contain an extraordinary amount of power. The villain wants to take these stars and become a Galactic Conqueror. The villain never gets all seven; some remain free. The star children turn out to be Baby Mario, Baby Luigi, Baby Peach, Baby Donkey Kong, Baby Wario, Baby Bowser, and Baby Yoshi. The last two were never captives; Baby Yoshi is still in the egg, and hatches at the very end of the credits.
In BlazBlue: Calamity Trigger, Ragna the Bloodedge is treated this way since he supposedly wields the Azure Grimoire. In the sequel Continuum Shift Noel gets this treatment after it's revealed that she is the true wielder of the Azure Grimoire and Ragna's Grimoire is a flawed imitation.
A variant occurs in Professor Layton and the Curious Village. Layton knows that he needs to find the Golden Apple of Baron Reinhold. What he doesn't know is that the Golden Apple is really Flora, the Baron's daughter.
BioShock 2 is centered around the quest of the player, a Big Daddy formerly bonded to a Little Sister, to find that Little Sister - who happens to be Big Bad Sophia Lamb's daughter and the messiah of the religion she founded. Subverted near the end, when she becomes a Big Sister and helps you fight your way out of the city, and is incredibly powerful.
In BioShock Infinite Elizabeth is this for no less than three factions in the game at various points: the player character, Booker DeWitt, has been instructed to rescue her from Columbia under the orders of a client offering to pay off his gambling debts; the main villains of the game, Father Comstock and The Founders, want to keep her imprisoned (and later, recaptured) so that she can one day take up Comstock's mantle and bring the apocalypse to "the Sodom below"; and by the end of the game, the Vox Populi are out to kill her simply because she was such an integral part of the Founder's belief system. During the ending, Booker's goals are subverted all to hell when it turns out that his memories have been badly mangled by dimensional travel, and he's not out to pay off his debts at all; he's out to rescue his daughter.
Burial at Sea revolves around Booker and Elizabeth trying to rescue an orphaned girl who was turned into a little sister. The girl appears very few times in the entire game.
Similar to the TRON: Legacy example above, Tron 2.0 had this in the form of Ma3a, who carried the correction algorithims needed for Jet and Alan to get back to the analog world. However, the terrible trio from F-Con were also seeking those algorithims in order to digitize an army into cyberspace and Take Over the World.
Ryu from Street Fighter is treated this way for most of his plot involvement. Bison is after him in Street Fighter Alpha to use him as a new host body while Seth wants to use his Satsui no Hadou to complete his bio weapon.
The Destined Children from Romancing Sa Ga 3 The Abyss Lords want them to open the gate to the Abyss so they can escape. Both also serve to summon the Destroyer to end existence if both are in the abyss at once. Abyss Lords used the Devil King for them to rule the world for 3 centuries before the Holy King sent them packing.
A humorous variant appears in Zelda II: The Adventure of Link. In one of the towns Link must visit on his quest, he is begged to recover a child, who has been kidnapped and may be found in a nearby cave. The reason it's humorous is because the game treats the child like any other inventory item - including having Link lift it over his head in his traditional Item Get pose.
In Mass Effect 3, the female krogan dubbed "Eve". Because of Maelon's brutal experiments conducted during the previous game, her fertility is no longer hampered by the genophage affecting all krogan, making her the key to finally developing a cure.
Commander Shepard can become this in the Synthesis Ending, as their cybernetic implants from the Lazarus Project make them the perfect mixture of organic and synthetic required by the Catalyst to kickstart The Singularity.
Charlie in Shikkoku No Sharnoth serves largely as comatose Macguffin to make Mary go through the plot. Except in the end, when she's actually an opponent.
In A Moment Of Peace, the subject of one of the gods' quests is a glowing entity named Gloria on the Mountain.
Barbie And The Secret Door has the Queen Unicorn, the most magical creature in all of Zinnia. Malucia is desperate to capture her and drain her magic.