Monsters work their way into our hearts in tons of ways. Some have art that grabs you immediately, some fill a niche you need in a campaign, some fight players in epic battles, and some have a tiny throwaway line in their monster entry that justifies the whole thing. But even with all that, I think these monsters made it to the list somewhat uniquely.
Kruthiks are reptiles, but you’d be forgiven for thinking they’re insects or weird chitinous dogs with spider legs. They best analogy I have is that they’re low-level Zergs. They happen in swarms, they’re startlingly fast, they can burrow, and the bigger ones even spit acid. I think they were first published in the catch-all Minatures Handbook, which seemed to contain monsters and classes Wizards wanted to make into miniatures but couldn’t because they hadn’t published them yet. They were justifiably forgettable until they were included in the 4E Monster Manual, where they got a little bit of lore that made them acceptable minions for a low-level villain or antagonists in a short adventure.
I didn’t care about kruthiks, at all. They didn’t seem fun, they didn’t seem unique, and I played Protoss anyway. I did collect D&D’s randomized miniatures, and while I didn’t want kruthiks I could use them as stand-ins for other things. One day I looked at my collection and realized I had six small kruthiks, three medium ones, and a large. I figured I might as well do something with them. At that time my campaign was already nearing epic levels, so the bottom-tier kruthiks didn’t appeal to me. But I could take how they looked, strip out the stat block, and use them an inspiration for something decent (so take a drink of a different beverage, I guess).
Scientivores were creatures that ate knowledge, in the same way that herbivores eat herbs and carnivores eat carnivals meat. I don’t know why I settled on scientivore instead of cognotivores or librivores, but that’s not important. The players met them in a demiplane made entirely of library, and the scientivores were slowly consuming the entire dimension. Unlike most monsters they weren’t a threat to the players or their allies directly, but defeating them was the mission the party had to accomplish, and nobody wanted to find out what would happen if they ate all the books and realized there was information in brains too.
They worked well, not least because of 4E’s excellent minion mechanic. They could swarm the party while still being a threat in a way monsters normally can’t. The first time they attacked, the players got a map of the area and five rounds’ warning so they could shore up and build their defense. The scientivores smashed open doors, burrowed through walls, and worked the party into a corner before reinforcements arrived (which, in retrospect, may have included Eligio). After the party fought them off, they developed a plan to destroy the entire hive at once, and that’s how we got this story.
The way they fell is still one of our favorite stories, but that only worked because they were viable enemies even before they first came onto camera. I still didn’t run a kruthik proper, and I probably never will, but without the creature and its miniatures we might not have had a library at all, and I’m pretty sure that ended up being one of my players’ favorite floors in that campaign.
In the Eight Arms and the Shadow Invasion, the players started off the campaign fighting shadow creatures, began fighting light creatures in Act 2, and ended up in a three-way free-for-all against both factions. The light-based enemies were shored up by jyoti, who brought a martial aspect to the fight without blinding everybody, enemy or ally, nearby. They were a decent CR for the party, such that the players could fight three or four of them at once in an ostensibly balanced encounter, and they were close enough to harpies and other winged creatures that I could use the minis I had on hand for them. They fit perfectly.
Enter Eligio, ice elemental warrior with a Wisdom of 4, who believed anything and everything you said to him. When he fought alongside the party and defeated the villain on that floor of the tower, he gained a level and sufficient will to ascend it himself. He showed up a few times from then on, usually allied with the party, and though he joined their enemies late in the campaign he died off-camera before they could fight him. Eligio became such an endearing character that he also showed up a few times in Delve Night, our 
My intention in the first Zelda campaign was to have a villain who was not Ganon. I thought a group of mid-level players wouldn’t be powerful enough to fight the actual Ganon, and I thought a different villain would lead to a more interesting story. Over the course of the campaign I realized how much the players really, really wanted to fight Ganon anyway, but I wavered on it because didn’t fit what I was doing. Come the final session, the final boss turned out to be really underwhelming and she largely went down without too much of a fight. The campaign wasn’t ending on a good note, and we still had some time left in our gaming block. In a pinch, I flipped through the books real quick to find a creature who kind of fit Ganon’s build, wasn’t too complicated, and sat at an appropriate final boss CR. The hezrou fit the bill, so I reskinned his stench as an aura of evil, the same thing that prevented the player from targeting him in Ocarina of Time.
I’d like to say this taught my players a valuable lesson about asking the questions to which they want answers instead of asking something similar and assuming other people understand their meaning, but that’s not even a little true. It also did not teach the players not to go to the grodair for help. Because they spent the campaign apart from any sort of information network and without a means to call for help, I gave them an NPC sage who could answer questions about monsters for them. Because the NPC was helpful, they immediately assumed it was an enemy plant, even though they didn’t assume that about anybody else who was assisting them. Instead they opted to deal with the insufferable fish rather than the NPC who wanted to help because the fish was exactly frustrating enough to be trustworthy.
But I ran a Zelda campaign, so I had to include their bat equivalent, keese. And since keese were one-hitpoint minions, I could throw them in pretty much at any level as a way to annoy my players whenever they showed up late for game too often. We also had an escalation of that mechanic, which we called super-minions: creatures who became bloodied after one hit and died after a second. It meant they weren’t completely invalidated by any persistent or automatic damage, but never so serious that they were a real threat except in the context of the monsters they accompanied. Fire bats, or here fire keese, were super-minions. If they took damage or hit an opponent, they lost their flame, and almost any damage dealt to a flameless keese killed it. The exception was fire damage, which healed them back up to full hit points (which, to be fair, was 2).
He dubbed the stranger “Señor Risco”, and to be honest I have no idea why. I vaguely recalled that “risco” was Portuguese for “rock”, and earth elementals spoke Portuguese because of some one-off gag from a previous session. A quick check now proves that’s nowhere near the correct translation, but whatever, the name stuck. We got Señor Risco a luchador’s mask, then realized he could not earth glide with the mask on, so he followed the party mostly hidden with only his head sticking out of the ground. From there the jokes kept piling on and he became something like a member of the party, perhaps even more than the cohort who was doing all of our healing. When the campaign ended he was thirty feet tell and he had taken the feats he needed to perform tag team maneuvers, which were mostly picking up the slowest members of the party and throwing them to (at) their enemies.
The Portalator was a shopkeeper who managed portals to various other planes and places within them. I think he was in the Abyss, and he came up when the party wanted to work their way to a demon prince who had been harassing them and give him what for. He was forward, personable, and maybe ever so slightly incredibly camp. From the very first word he uttered, he was clearly not a typical slaad and became unique enough for the players to recognize and dread him from them on. He turned against the party for reasons I honestly don’t fully remember, and at the end of the campaign’s second arc he managed to kill the cleric with a save-or-die right after she used one against his team. They got their revenge against him in the third arc…I think. I’m not sure they ever found the body.
When I was working on the second Zelda campaign, I decided one of the themes was going to be animals, not least because I had found a series of really neat pictures of pseudo-magical creatures I could leverage. The players met spirits, each of which took the form of an animal, and allied with them to gain magical powers. When it came time to design the actual plot of the campaign, I decided they should have a leader the players could help. I didn’t want something simple like “lion, king of beasts”, I wanted something that represented as many animals as possible. I remembered chimera, the word more than the actual creature, and I found a picture that looked like a regal somebody with a motley combination of animal parts so we could have our version of Princess Zelda.
In that context, my players actually have encountered several brains, and some of them occurred outside their enemies. The first birthday session I ever celebrated involved pitting the players against video game villains, and the role of Mother Brain was played by a brain in a jar on the top of a clockwork giant of some type (take a drink). In the Great Tower of Oldechi, the players spent an entire level inside a body, and at one point they tapped into its central nervous system to speak with the brain directly. I once had a campaign villain planned who gained psychic powers because her brain had been replaced by something else, though the players managed to dodge it.