Dr. Bunsen Honeydew of Muppet Labs. Where the future is being made today.
Dr. Emmett Lathrop “Doc” Brown, of course. 
Follow up: Walter White.
Honorable Mention: Walter Bishop. John Noble really gave him some great personality and depth.
Ah yes, the very plausible fan theory that Pinky was the real genius:
Henry Mulligan of Mammoth Falls.
No one makes a better -inator. Should learn to avoid adding a self-destruct button though.
How about Diskworld’s Leonard of Quirm.
I nominate the legendary Vincent Price as Dr. Phibes.
This one was a two-parter.
The Abominable Dr. Phibes
Dr. Phibes Rises Again
I’ll go with Dr. Hugo Strange as he was portrayed in Detective Comics back in 1940. Insane, evil, greedy…when they revived the character in the 1970’s it was initially promising but they have taken him in directions less mad scientisty IMO. There was another early Batman foe, Dr. Death, who had some kewel mad scientist action going on. His stories are more notable, though, for the henchmen that Batsy straight up kills.
C.A. Rotwang* from Fritz Lang’s Metropolis, played by Rudolf Klein-Rogge.
The original Mad-Scientist-Who-Lost-A-Hand. His cinematic laboratory inspired Dr. Frankenstein’s in the movies. His dwarf assistant arguably inspired Fritz and Karl and Ygor and a host of other unusual assistants (right down to today’s Minions). Plus he had the first really cool robot. He was always a bit on the edge (he created the robot to “bring back to life” his lost love, Hel, who had married Joh Frederson, Master of Metropolis), but at the end of the film he does go completely mad.
Runner-up – Dr. Pretorius in Bride of Frankenstein, played with aplomb by Ernest Thesiger. A guy who can’t be ruffled by the appearance of a brought-to-life creation while he is himself in the process of robbing a tomb is just incredible. (Of course, he’d already created his own creatures, although we don’t know that by this scene.)
Jules Verne had some Mad Scientists, but it was his son, Michel, who really loved them – Xirphan Xirdal in The Meteor Hunt, Marcel Camaret in The Barsac Mission.
My favorite, too…
Oh, Dr. Emilio Lizardo is the definition of a mad scientist. Still one of my favorite characters.
For new ones, a shoutout to Gene ray, who may now be deceased and his Time Cube, which has been a fixture on the web for years (sadly, the original site is gone, but google around if you’ve never seen it, I’m sure that it is archived somewhere.
For fiction, Kevin Andreyasn of Schlock Mercenary webcomic is my favorite. Hey, he’s invented a galaxy-changing mode of travel, cloned himself, traveled in time, and been killed at least five time (he got better).
In real life you have Barry Marshall:
the very earliest reference I’ve found to a real-life “Mad Scientist” refers to Constantine Samuel Rafinesque (1783 – 1840), a polymath and autodidact. He was called both an “eccentric genius” and “mad scientist” in his time.
The clincher? He was Professor of Botany at
[spoiler] Transylvania University !!!
For real.
Of course, it was Transylvania University in Lexington Kentucky, so no crumbling castles or vampires, but still, it’s significant.[/spoiler]
Doctor Cockroach from Monsters vs. Aliens, movie and TV show. Fifty percent cockroach, fifty percent human, and proud of it. Sort of like “The Fly”, except he embraced his new identity.
Well, to be fair, Dr. Cockroach had a very human mouth and could monologue and expostulate and go “Bwa-ha-ha!” all he wanted.
The original Fly, and his Son, and (in the final transformation) the David Cronenberg “Brundlefly” (and Chris Walas’ “The Fly II”) — couldn’t. No sound-producing mouthparts. This puts a severe damper on Mad Scientist-ing, and suggests a profound disappointment with their lot.
(Yeah, I know that the flip sides of the David/Al Hedison Fly and the really poor sequel “Son of the Fly” did have speaking mouths, but they were attached to the bodies of flies, and couldn’t actually DO anything, except speak in high, squeaky voices (“Hellllllp Meeeee!”) Cronenberg’s Fly didn’t even get that – he ansorbed his Fly, leaving no Fly Complement. )
Anybody else remember this guy?
Dr. Lizardo was great, but these days I’m digging Rick, from Rick and Morty. Everyone’s favorite alcoholic dimension-hopping gun-running sociopathic grandpa.
But even before the first appearance (non-bald, BTW) there was:
"The Ultra-Humanite is the first supervillain faced by Superman, and among the first supervillains of the Golden Age of Comics. He was designed to be the polar opposite of Superman; while Superman is a hero with superhuman strength, Ultra-Humanite is a criminal mastermind who has a crippled body but a highly advanced intellect. The Ultra-Humanite served as Superman’s nemesis until Lex Luthor was introduced in the comics.
The Ultra-Humanite represents one of the most significant threats to 20th century incarnations of the Justice Society. The origins of the super-criminal known as the Ultra-Humanite are shrouded in mystery. Even he claims not to remember his true name or appearance and attributes his vast intellect and mental prowess to scientific experiments of an unknown nature.
A fiendish *** ‘mad scientist’*** …"
(The above is from Wikipedia, with my emphasis added.)
Prior to his later incarnations,he was sometimes shown as nearly bald, sometimes entirely. Again, according to Wikipedia.
If engineers count, then my favorite real-life example is Nikola Tesla. He was certainly mentally ill, he gave all the appearance of being the modern-tech version of a wizard, and his legend has inspired a lot of science-woo craziness (and at least one Dope-trope).
For actual scientists, Wilhelm Reich.
Hair-impaired seems to be a mad scientist thing. In fact, these guys and the Ultra Humanite all look enough alike that they could be related.