You're not the horse. You're the barely visible kid on the horse.
General:
Bosses tend to be much bigger than the protagonist in a lot of games, especially 2-D side scrollers.
Specific games:
Played with in Searching for a King (1984), an educational Apple ][ game in The Baker Street Kids series based on The Bible, in which Jamie plays the role of David, while a short boy on leg-like stilts plays the role of the giant Philistine.
Most of the bosses in Bayonetta fought by the heroine are the size of skyscrapers (at least!). Ironically, to humans, Bayonetta is quite the Statuesque Stunner.
Cuphead and Mugman are always much smaller than their opponents as well as only being able to take a few hits, while the bosses can take numerous and dish out loads of Bullet Hell in return.
Ever played Dark Souls? Nearly every boss fight is against something massively bigger and more powerful than your puny undead warrior character. But no matter how mismatched or daunting the fight may seem, you can win with clever tactics, great reflexes and a Determinator attitude.
In the final route of Duel Savior Destiny you're required to beat Downy with Sel. Not only is your opponent way stronger in terms of story, he's also at a much higher tier than the character you have to use. In fact, Selbium is actually significantly weaker than the normal units you use, though his style matches up against Downy fairly well.
Eastern Exorcist plays this straight with most of the bosses being gigantic demons, several times larger than the player heroes, in both campaigns. The Mirror Boss fights the same size as the player characters can be counted on one hand.
You can get mods for Empire: Total War and Napoleon: Total War which allow you to play as the tiny emergent factions, such as Scotland, Punjab, or Mexico. Surpassing the major world powers is very difficult, but certainly doable.
Enter the Gungeon has the Sling weapon as an allusion to the trope namer. It's stated that the weapon should only be used as a last resort but it does decent damage the larger enemies are, and gives a massive 4X boost to its already respectable damage when fighting a boss.
Extinction have your human hero, Avil the Legendary Giant-Slayer, taking on kaiju-sized monsters called the Raveni terrorizing the land throughout the game, which you slay aplenty in various levels. The Raveni's equally-vicious offspring, Jackals, are larger than humans as well.
In Fallout 4, the Railroad is made up of a loose confederation of idealistic Wastelanders operating from underground safehouses, with a handful of Synths and scientists of note. Their main rivals, the Institute, are arguably the single-most powerful faction in the entire Commonwealth, with vast stockpiles of resources and a monopoly on advanced technology. Then the Brotherhood of Steel turn up with their Cool Airship and armies of knights in Powered Armor. It's possible for the Railroad to smack down both of these factions in their ending.
One possible outcome features the Minutemen, an army of wastelander militia with weapons which qualify as jury-rigged Schizo Tech, versus the Brotherhood of Steel with their Vertibirds and high-tech armoured Knights. Depending on how much you built up the Castle, it can either be a hard-won fight or an absolutely humiliating thrashing for the Brotherhood.
Two major fights in Fate/stay night. The first on the horribly unbalanced seeming nature of the fight is Shirou Vs Berserker which is won due to an 11th-Hour Superpower projection of Caliburn plus Saber's assistance. The second is less jarring in appearance but a far bigger upset in actuality when Shirou takes down Gilgamesh essentially singlehanded, chopping his arm off and about to deliver the final blow before the Grail opens on him and Archer has to save Shirou from trying a Taking You with Me.
Final Fantasy XIII. The Adamantoises and Long Gui are ridiculously huge compared to the party.
Hell, just about everything is significantly bigger than your party. Behemoths, anyone?
In House of the Dead, there's always at least one fight, most times more than once, where the two not-so-physically-imposing AMS agents face off against a giant behemoth (Chariot in the original, Strength in II, Death in III, and Temperance in IV).
The plot of inFAMOUS 2. It begins with The Beast, an incredibly powerful Conduit, nearly killing the main character, requiring him to retreat to increase his powers. Once you finally confront him again you can pull a Heroic Sacrifice and use the RFI to kill all conduits on the planet, sacrificing yourself to stop The Beast from annihilating the human race.
The Legend of Zelda is all about a small boy/young man named Link who defeats Ganondorf, a large man from the desert, who often becomes a giant boar monster named Ganon. Most bosses in the series also qualify.
The bossesApocalypse, Onslaught, Abyss and Galactus in the Marvel vs. Capcom series.
In Metal Gear Solid 4: Guns of the Patriots, you have the battle between the outdated, and damaged Metal Gear Rex, versus the Anti-Metal Gear unit, Metal Gear Ray. Despite having the better machinery, Snake still manages to defeat Liquid and his Ray. However, it's only because he let him win.
Monster Hunter. Big scary wyvern (or gorilla, or dragon, or Giant Enemy Crab, etc.) the size of a truck takes on a human. The human, with their advanced armor and weaponry, wins regularly (though it helps that said gear is made from another one of said beasts.)
No More Heroes and its sequels: We have bosses using huge laser cannons (Speed Buster), a huge sentient earthquake machine (Letz Shake), a crazed tycoon that first bloats into a hulking bloke and eventually inflates to the size of a blimp (Jasper Batt Jr.), and gargantuan offworld monstrosities that can only be fought with a mecha (the outer space monsters that are part of FU's army).
No Straight Roads includes battles against a DJ that turns into a giant, a giant digital mermaid, a child prodigy's mother that's already turned giant, and a cyborg admiral that pilots a robot dispenser.
In Mike Tyson's Punch-Out!!, protagonist Little Mac fights a series of boxers who are all at least twice his size.
The first two stages against Otto Destruct in Ratchet & Clank: Size Matters shows him towering over the titular heroes. In the third and final stage, though, the size differences are similar.
Leon is the David to the Gigantes' Goliath. In the former's favor, there's usually something that helps him in each case: A dog in the first Gigante battle (provided he saved him, otherwise he'll be out of luck), a boulder trap in the second (which is also optional, as another route can be taken to progress in the game), and a lava trap for one of the Gigantes in the third.
An interesting example happens in chapter 3-4. Common mooks that both Ada and Leon can dispatch very easy become more dangerous as the player has to play as the civilian Ashley. Leon is already taller than her and the male mooks are taller than HIM! Furthermore since Ashley has no combat ability seeing Ashley facing one is a sight to behold.
The entire premise of Shadow of the Colossus. The hero, an ordinary young man, fights a series of creatures ranging in size from a large bull, to a literal skyscraper... and wins, mostly due to being clearly Made of Iron. Plus some help from a horse that's apparently Made of Adamantium.
Shantae: Half-Genie Hero: Shantae's much smaller than her biggest foes, such as the Tinkerslug, the Mermaid Queen, and Wilbur - all have the screen zoom out to show how large they are. The smallest of those would possibly be Tinkerslug, which is a whole ship that can fit at least 10 Tinkerbats, which are approximately Shantae's size, just on a third of what's visible of its top surface.
Shining Song Starnova revolves around the conflict between Starnova (a small, recently-formed idol group whose members are complete newbies or washed-up has-beens) and Quasar (a massive, highly-experienced and well-funded idol group which has dominated Tokyo’s entertainment industry for over a decade).
The Simpsons: Bart vs. the Juggernauts: All of Bart's opponents are grown, muscular adults. It's even brought up in-game when Monroe points out that Bart is, you know, 10-years old, and even the smallest of the Juggernauts is an amazonian woman weighing in at around 160 lbs. Most of them are much bigger.
Somewhat of a staple for final bosses in later games which adopt the Monster of the Week formula, especially Dark Gaia who's roughly the size of a continent. That Sonic usually handles such enemies in his Super Mode however removes any pretense of him being at a disadvantage.
Ibuki, a tiny lightweight weak but skilled female fighter who stands at 5'3 and weighs 101 pounds, but battled the massive 8 foot Abigail in the latter's story mode. The height difference is remarkable and he is taller than a fully standing Ibuki while crouching on his knees.
Ibuki also has a battle with final boss Gill, who while massive in his own right at 6'10 isn't as tall as Abigail, but outweighs Ibuki by an entire 644 pounds, and no that massive weight difference isn't caused by Obesity. Those Psycho Lariats are going to hurt.
Her rival battle teaming with Rolento against King and Craig Marduk in Street Fighter X Tekken is based on this. While Rolento is no small man, being a full head taller than Ibuki, King and Marduk are both among the tallest humans in Tekken. Both dwarf Rolento and Ibuki herself looks pint sized in comparison to them. In the cutscene from the Tekken character's size Ibuki has to jump to try and hit Marduk in the head, which he easily proceeds to knock back the petite ninja.
The final boss fight of Struggling pits the hero against a giant... duck?
Depending on the player's choices in the first game, the three-kilometre long PACT dreadnought Legion can finally meet its end when the Sunrider, a ship less than a quarter of its size, fires its Vanguard Cannon straight down the barrel of the Legion’s own Wave-Motion Gun at point-blank range.
In Sunrider 4: The Captain's Return, High Admiral Kuushana has every possible advantage over Kayto Shields. She has a better Ryder squadron, a bigger and more heavily armed flagship, superior strategic skills, and unlike Kayto, who's waging a one-ship war on a Galactic Superpower, she has a 10,000-ship-strong navy at her beck and call. Most confrontations with Kuushana end with Kayto having to beat a hasty retreat, but at the climax of the game, his forces manage to shoot down her Ryder, sink her flagship, and wipe out half her navy in one fell swoop.
Generally averted in Sword of the Stars. Superior micro will only take you so far in a tactical encounter when the enemy outnumbers or outmasses — or both! — you, at least in a straight fight as opposed to repeatedly throwing ships at the enemyto wear them down. To reinforce the need to outnumber, you get extra command points for every so many ships of each class more than the enemy you have, up to a certain limit, allowing you to field more ships than the Arbitrary Headcount Limit would normally give you. Get enough and you can deploy extra dreadnoughts. While destroyers can occasionally beat dreadnoughts, this relies on swarming and the dreadnought-user failing to include light weapons on his ships and is far from foolproof.
In Team Fortress 2, the Scout and the Heavy have a fierce in-universe rivalry. The Scout is a beanpole-thin, short guy, while the heavy is a huge muscleman. Of course, which is the hero and which is the villain depends on which team each is on, and whether or not the Scout can actually defeat the Heavy in a fight depends on how good (or how poor) a player is using one of them, but one good example where the Scout does win occurs in "Meet the Scout".
Transformers: Fall of Cybertron ends up having this on both ends. For Autobot segments, most anything that tries to stop Grimlock (who dwarfs most everything in the game) is the David to his Goliath, particularly with the target of his Roaring Rampage of RevengeShockwave, one of the smaller characters in the game that doesn't even come up to Grimlock's knee, but is much smarter than his adversary, though it isn't enough to stop him. For when the player is the David, using Jazz against Bruticus, the former being the shortest playable character in the game, and the latter being by far the largest.
Kishima Kouma as Goliath vs. Nanaya Kirei as David. Kouma has essentially no skill whatsoever because he doesn't need any. His skin is tougher than steel, he can punch through trees effortlessly and doesn't tire. Kiri is essentially the most skilled assassin on Earth. Unfortunately, he's an assassin and not a magus or anything like that, so he's reduced to hammering at one side of Kouma's neck and then hitting the other to try and break it. The difference in skill is so huge that his opponent doesn't even realize he almost died with that attack. Key word: Almost. Goliath wins. Foregone conclusion, though, if you've played Tsukihime.