Alternate Aesop Interpretation: The well-written but nonetheless anvilicious episode "Inherit the Wheeze" focuses on the message "Smoking is bad." However, since the Brain only became addicted as a result of clearly painful experiments the lab forced him to go through, which he didn't enjoy one bit, the message "Experimenting on animals is cruel" comes across much more powerfully.
Alternative Character Interpretation: Sure, "one is a genius and the other's insane". But who is insane? The megalomaniac bent on world domination or the one who saves the world every night and seems to be a pretty happy guy? Never mind that Pinky is much more literate than Brain, or the few times Pinky has gotten much further than Brain in taking over the world, even becoming President of the United States once. In contrast, many of Brain's evil schemes run on Insane Troll Logic, and even while some of them can be excused since they live in a crazed cartoon universe, they way he goes about achieving them is often stupid enough that Failure Is the Only Option anyway. Word of God has confirmed that the theme song leaves it open to the viewers to decide...
Broken Base: There are those who prefer Pinky's new voice; however, some fans did find his speech impediment early on to be endearing.
The "Pinky & the Brain Split Up" skit in The Nostalgia Critic's review of "The Purge" was either hysterically funny (due to both of the titular character's voice actors returning to reprise their roles, and thus saying some decidedly unsavory things), or was needlessly cruel to a character who proceeded to have his spirit crushed in the saddest way imaginable.
The mice made cameos in the two prime-time Tiny Toons specials, and both cameos had them in scenes prominently featuring Elmyra. Apparently, this must've been where they got the idea for the much-reviled RetoolPinky, Elmyra & the Brain.
In addition, the episode "Pinky and the Brain and Larry" became this after Elmyra became the third character in the Retool.
Snowball's last appearance, "Brainwashed Part 3", aired right around the time his voice actor died.
The episode where Pinky and the Brain create a papier-mache replica of the Earth, so that they can convince everyone to relocate and they can take over the real world. The background music during the montage of them building the thing? Dvorak's Symphony no 9 "From the New World."
Frankly, there's enough of these that one starts to wonder if the show was even truly made for children.
Much like parent show Animaniacs, P&TB frequently took quite a few jabs at Disney, yet ended up as one of the last shows added to the Toon Disney lineup. It was last seen working the late shift on weekends during the first few months of the existence of successor Disney XD.
One episode, a Winnie-the-Pooh parody, has, as its Eeyore stand-in, a donkey named Algore, a parody of...well, guess. The Brain quickly realizes that the rambling Algore is quite literally full of hot air, causing the occasional warm breeze. Cue jokes about Al Gore being the realcause of global warming.
In "Broadway Malady", The Brain's show, "Angst: The Musical", has a number called The Schadenfreude Polka. A musical with a number about Schadenfreude? How ridiculous.
In "The Real Life" Brain is informed that "no one listens to vinyl anymore.". As of the late 2010's, vinyl has been making a comeback.
In "A Meticulous Analysis of History" Pinky mentions "the former of governor of Arkansas" with a picture of Bill Clinton in his underwear, referencing a claim that Clinton wrote his underwear off as tax deductible, made hilarious by the Monica Lewinsky scandal a year later.
The infamous "And Larry" now sounds quite a bit like "And Peggy."
Pinky and Brain disguising themselves as a cow to go to China in "Around the World in 80 Narfs", which had Brain posing as the cow's head, is funnier in light of computer company Gateway's commercials featuring a talking cow voiced by Brain's voice actor Maurice LaMarche.
True, each of them had female love interests, but a DVD featurette even acknowledged that the show was about the "love" between the duo (they were probably talking about platonic love, but it's easy to misinterpret that). And in the episode "Brinky" the two inadvertently mixed their DNA together in a cloning machine, essentially having a child with each other.
That whole episode exaggerated the couple thing Up to Eleven, infinity, and beyond. They both fell into the family roles immediately and Romy addressed them as "my two dads". They went through all the cliche marriage problems of an after school special. At the end of it, Pinky asked Brain if they could have another. Why, even the episode title is a ship name: Brinky!
There's also the episode "Pinky Suavo", where Pinky, through an accident with Brain's "Personalitron", becomes a charismatic, suave, romantic figure loved by everyone. And we mean everyone. Watch Brain's initial reaction to the new Pinky and just try to deny that he's suddenly developed at least a mancrush on him.
For a brief moment in "You'll Never Eat Food Pellets In This Town Again", they sleep in the same bed.
Pinky also often dresses up as Brain's wife, neither can live without the other (as seen in "This Old Mouse" and "A Pinky and the Brain Halloween"), Pinky's given up his soul for Brain and Brain's given up the world for Pinky, and in "Just Say Narf" there's a scene where he actually tries to seduce Brain on a bench. Honestly, the sheer amount of Ho Yay moments with these two is staggering.
The subtext between them gets even more paper-thin in the comics, with more questionable Are You Pondering What I'm Pondering? lines ("I think so, Brain, but this time I get to play the dishwasher repairman!"), Brain proclaiming that he could kiss Pinky out of gratitude (and Pinky being completely fine with the idea) and Pinky's reaction to Brain apparently severing their friendship is to attempt suicide. And then there's this infamous moment...
Magnificent Bastard: Brain on occasion. Usually when he's trying to save the world for a change.
Memetic Mutation: It is difficult to say "What are we going to do tonight?" to someone who watched this show without getting "The same thing we do every night, try to take over the world!" as a response.
Especially Brain's nightmare from the first part of the "Brianwashed" trilogy.
Tastes Like Diabetes: In the episode "Brain Drained", one of the interviewees suggests that the Pinky and the Brain TV show should drop the world domination aspect and be a Nick-Jr.-esque children's show called "Pinky-Winky and Brainy-Wainy".
Pinky, Elmyra & the Brain. Not only do the fans hate the series, but also the writer; Peter Hastings not only wrote an episode of the original series predicting the series' downfall because of the executives' demands ("You'll Never Eat Food Pellets in This Town Again"), but later left Warner Bros.
To a lesser, yet still reviled, extent, when the show was rerun on Nickelodeon, the channel superimposed their logo onto various objects in every single shot of the intro. Nobody liked it.
Values Dissonance: Brainania has a touch of this. This is partially from the portrayal of South Pacific Islanders as naive and easy to dupe, and partially because foreign aid is no longer seen as the Acceptable Target it once was.
The Woobie: Both mice are examples in their own ways.
Pinky, despite his cheerful personality, gets hit with Break the Cutie quite a bit (like when he was crying in "The Family That Poits Together, Narfs Together" when he remembers being taken away from his family), and he could really use a hug at times in the Christmas and Halloween special episodes.
Brain tirelessly works to achieve his ambition, but is constantly thwarted by various means. It may be that his gene-splicing experience has deprived him of much of his emotional sensitivity, hence his cold and jerkish tendancies. He slips into Jerkass Woobie territory on several occasions when he realizes how badly he treats Pinky and gets upset about it. It also doesn't hurt that he's capable of pulling off some serious Puppy-Dog Eyes — and does so in the opening theme.