These are what we call the 'YMMV items.' Things that some people find in this work. We call them 'your mileage might vary' because not everyone sees these things in the same way. This starts discussions in the trope lists, a thing we don't want. Please use the discussion page if you'd like to discuss any of these items.
After you make it past the preliminaries in Kaiba's tournament, you'll duel Shadi, the fifth opponent overall. While the previous four opponents scaled up in difficulty, Shadi is a noticeable step down, having monsters with stats in the hundreds, and not having significant fusions nor magic/trap cards in his deck. He's pretty much the only opponent past the early game you're guaranteed to not need to grind for.
When you return to the past, the first mandatory opponent is the mage soldier, whose monsters only have stats in the mid thousands, as well as no significant fusions nor magic/trap/equip cards. He's much weaker than the past few opponents you dueled in Kaiba's tournament, as well as the opponents to come.
When you return to the past and must retrieve the Millennium Items from the high mages in the shrines, High Mage Secmeton of the sea shrine and High Mage Martis of the desert shrine will come off as this, especially if you dueled the other, more difficult high mages before them. Secmeton uses a whole deck of water monsters, the strongest of which, Crab Turtle and Suijin, only have 2500 attack each(boosted to 3000 in the sea),and they're vulnarable to thunder monsters, meaning if you have acess to Twin Headed Thunder Dragon, which you almost certainly do if you've made it this far, he won't stand a chance. Instead of having monsters in the high 2000s or even 3000s that get powered up by his field, Martis uses powerful fiends and spellcasters (such as Summoned Skull and Skull Knight), that while still strong, do not get the field power bonus the strongest monsters of the other high mages have. This results in him fielding significantly weaker monsters than what the other high mages are using against you. The lack of strong monsters boosted by the wasteland field can be blamed for his odd monster choice, as no monster in the game has an attack over 2200 that is also boosted by wasteland.
In the endgame gauntlet, the second opponent (or first if you defeated Seto 2), Sebek, is much easier than the high mages you dueled and defeated, as well as easier than the opponents to come. He uses machine and beast type monsters, with the strongest being by far a Metal Zoa (which while it has 3000 attack, you have already defeated opponents fielding stronger monsters than this), and while dueling him on a yami field, which does nothing to boost his monsters. Most of his remaining monsters only have slightly more than 2000 attack, and he has no significant magic/trap cards nor equips.
Ensemble Darkhorse: The Meadow Mage. He's just a mook you only see on one screen in the game, yet he's the character that's remembered and talked about the most. With his amazing card drops, including giving most people their first Meteor Black Dragon, people have fond memories of extensively dueling him and gaining the cards that allowed them to finally beat the game.
Game Breaker: The magic card Raigeki, which just like in the TCG, destroys all of your opponent's monster cards with no cost to you. The major reason this is such a game changer is besides clearing your opponent's field, it leaves them open for a direct onslaught from the monsters on your field, which can leave their lifepoints severely reduced while being left in the weakened position of a monsterless field, if your direct attack didn't wipe them out completely. A single Raigeki can break a stalemate and win you the duel in just that turn, and just like any other card, you can have three of them in your deck. Having multiple Raigekis can be vital to surviving the endgame, especially if you don't have any Meteor Black Dragons.
High Mage Kepura is the most difficult of the high mages you'll face, and is as difficult as what you'll face in the endgame, using Gate Guardian powered up by the meadow you duel him on. With an attack over 4000, it'll take just two direct attacks from it to be defeated. Even the Meteor Black Dragon alone won't gain you victory here.
Seto 3 is also this, being the most difficult opponent in the game, having Blue-Eyes Ultimate Dragon and nearly every other extremely powerful monster, as well as the most powerful magic and trap cards.
Unwinnable by Insanity: When trading with another player, you're not required to put up the same amount of cards the other player is trading (nor have to put up any card at all). As such, it's possible to trade all your cards in your chest, and while the game does not allow you to trade cards that are in your deck, the game does not disallow you from exiting the build deck screen with less than 40 cards in your deck. So if you were to trade without 40 cards in your deck, and traded enough cards away, you would not have enough cards left to fill out a 40 card deck. And since you can't have 40 cards in your deck, the game will not allow you to duel anyone, thus preventing you from being able to play farther and preventing you from being able to get more cards to fill a 40 card deck again. The only ways out of this are to have enough starchips from beforehand to buy enough cards to fill out a 40 card deck (which considering the insane prices, is very unlikely), or get more cards from a player in a trade. Of course, the player would have to be intentionally invoking this, as there's no reason to exit the build deck screen with an incomplete deck, nor a beneficial reason for trading away all your cards to another player without getting anything in return.