The quintessential mad scientist. Without ever explaining why, Simon Barsinister is set on using his inventions for money, power and the destruction of Underdog. His henchman is Cad.

Simon's voice (Allen Swift) was an imitation of Lionel Barrymore's, and Simon's hulking henchman Cad (Ben Stone), who spoke like Humphrey Bogart.

His green-tinted skin, oversized bald head, dark bags under his eyes and short stature are defining features. 

"Simon Says …." accompanies every evil scheme.

Merriam Webster’s Collegiate Dictionary supplies this definition:

Main Entry: bar sinister
Function: noun
Date: 1823
1 : a heraldic charge held to be a mark of bastardy
2 : the fact or condition of being of illegitimate birth

Simon was introduced in the single episode short Simon Says on October 10, 1964. He also stars in:
Go Snow
The Big Shrink
Weathering the Storm
The Forget-Me-Net
Simon Says "No Thanksgiving"
Simon Says "Be My Valentine"
The Ticklefeather Machine
The Big Dipper
The Phoney Booths and
The Vacuum Gun

The model gangster, a wolf in a pin stripe suit. No match for Underdog, but yearns to be the number 1 crook. His voice (Allen Swift)  sounds somewhat similar to the Count from Sesame Street. His henchman is Mooch.

Riff Raff was inspired by cinema star George Raft who played many gangsters and always talked out of the side of his mouth.

Introduced on November 7, 1964 in The Great Gold Robbery and also stars in:
From Hopeless to Helpless
Just in Case
Pain Strikes Underdog
Guerrilla Warfare
Riffraffville
with a supporting role in the Vacuum Gun.

Overcat

Underdog's alien feline enemy with similar powers. Overcat steals all of Earth's cows after planet Felina's milk wells run dry.

Starring in Underdog vs. Overcat (and vows to return).

Tap Tap the Chisler

A thief and diamond cutter who looks exactly like Underdog and commits crimes while impersonating Underdog. Tap Tap can always be identified by his cigar and lack of rhymes.

Supports Riff Raff in From Hopeless to Helpless and stars in the one segment sequel Tricky Trap by Tap Tap.

Fearo the Ferocious

A spoof of King Kong, taken in chains by Underdog from his island for a ratings booster show with Sweet Polly Purebread. After terrorizing Calmed with bananas and taken home by Underdog.

Starring in Fearo.

Wicked Witch of Pickyoon

Your basic evil, spell casting witch with an all knowing magic mirror. She has enslaved the people of Pickyoon.

Starring in the cartoon of the same name.

Zot

Alien race of super strong three-eyed people try to capture Underdog and force him to marry the King Klobber's daughter. 

Starring in Zot.

The Bubble-heads

An underwater city Mal-de-Mare ruled by the Emperor who is in turn ruled by the Empress. Intent on conquering the surface world, destructive machines are put into play. The Bubbleheads also control all manner of giant sea creatures.

Starring in the Bubble-heads with a guest appearance in the The Flying Sorcerers.

Batty Man

A villain with the looks of a vampire. He and his batty men control hundreds of thousands of bats which are used to steal in mysterious ways. His henchman is Georgie.

Starring in Batty Man, he is also featured in the Vacuum Gun.

The Electric Eel

A big bad bald guy with a shocking attack. He is featured in A New Villain and also featured in Vacuum Gun.

The Magnet Men

A race of alien mechanical men.

Featured in The Magnet Men and a cameo in The Flying Sorcerers.

The Cloudmen

An alien race of ghostlike clouds. All are seeking silver linings. 

Featured in The Silver Thieves.