Star Wars wouldn't be complete without the "war" part of the story. The original trilogy had the plucky Rebel Alliance fighting the tyrannical Galactic Empire, while the prequel trilogy introduced a new antagonist for its telling of the Clone Wars: the Confederacy of Independent Systems.
Seeking independence from the Republic, thousands of systems seceded and united under the CIS banner, led by Count Dooku and funded by the galaxy's major corporations. While merely pawns of Darth Sidious, most of the villains encountered in the prequel era had pledged allegiance to the Separatists; let's look at which were the vilest of the lot.
10 Osi Sobeck
Sobeck, a member of the reptilian Phindian species, was the warden of the Citadel; a Separatist prison designed specifically to hold captured Jedi. During the Clone Wars, the prison held a Republic contingent commanded by Jedi Master Even Piell and Captain Wilhuff Tarkin, prompting a rescue mission led by Obi-Wan Kenobi and Anakin Skywalker. Callously shooting any droid who showed signs of incompetence, Sobeck led an increasingly desperate effort to recapture the prisoners, but was ultimately felled by Ahsoka Tano. A deserving end for the cruel jail-master.
9 Nuvo Vindi
A scientist/biological warfare expert hired by the Separatists, Vindi attempted to recreate the extinct "Blue Shadow Virus" as a bio-weapon for use against the Republic. Stationed in a secret lab on Naboo, Vindi intended to spread the completed virus across the planet and eventually the entirety of Republic space. Showing greater regard for the "life" of the virus than any of its intended victims, Vindi was ultimately stopped by the usual team of Skywalker & Kenobi, though not without a few casualties from a contained outbreak of the virus.
8 Poggle The Lesser
A high-ranking member of the Geonosian Hive and the Separatist Council, Poggle the Lesser was a weapons manufacturer by trade. It was the factories owned and operated by him that actually built the droid armies which the Separatists used to wage their war; even worse, it was Geonosian scientists who first crafted the blueprints for the Death Star.
Due to the violence inflicted by his creations, Poggle bears great responsibility for untold death and suffering throughout the galaxy. Fate eventually caught up to the Geonosian, however, when he was slain by a newly turned Darth Vader alongside the rest of the Separatist council on Mustafar.
7 Admiral Trench
Trench, a member of the arachnid-like Harch, was one of the most revered and highest ranking Admirals in the Separatist Navy, known both his strategic skill and his ruthlessness. Seemingly killed when his flagship was destroyed over planet Christophsis, Trench proved more resilient than expected; he returned to the battlefield, outfitted with extensive cybernetics to repair the wounds inflicted on Christophsis. Trench then lead the Separatist forces in their sieges of planets Ringo Vinda and Anaxes; the latter battle revealed the depths Trench would go, as he plotted to detonate a bomb that would blow apart Anaxes as a last ditch attempt to secure victory. However, the Admiral's plan, and his life, were prematurely ended by Anakin Skywalker.
6 Riff Tamson
Separatist ambassador to planet Mon Cala, Tamson discretely undermined the relationship between the planet's two native species, the Mon Calamari and the Quarren. At the order of Count Dooku, he even assassinated Mon Calamari King, Yos Kolina. Tamson performed all of this with the promise that he and his people, the shark-like Karkarodons, would be the new rulers of Mon Cala at the behest of the Separatists. An arrogant, sadistic tyrant who didn't even try to pretend his actions were for the greater good, Tamson met a deservedly brutal end; blown to pieces by a bomb of his own making.
5 Lok Durd
A Neimoidian weapons engineer, Lok Durd was the inventor of the "Defoliator," a mortal-like device mounted atop Separatist tanks whose ammo would destroy organic matter while leaving machinery intact; a clever, if brutal, innovation when your own arm is staffed entirely by droids while the enemy soldiers are flesh-and-blood. What earns Durd a spot on this list is the means he went about testing his weapon. Occupying the planet Maridun, Durd intended to test the Defoliator by wiping out a colony of pacifist Lerman settled on the planet. Thankfully, the weapons test was thwarted by the combined efforts of Jedi Anakin Skywalker, Ahsoka Tano, Aayla Secura, and clones Rex & Bly, who took Durd into Republic custody.
4 Count Dooku
The public leader of the CIS, Count Dooku of Serenno proclaimed himself a political idealist fighting against the Republic's corruption, but in truth was anything but. In order to secure funding for the Clone Wars, Dooku got into bed with the very corporations who had caused the corruption he'd claimed to oppose. He also ordered or participated in numerous atrocities throughout the war themselves, including ordering the massacre of defenseless refugees.
Of course, the most damning part of Dooku's actions was that he was truly the Sith Lord Darth Tyranus, apprentice to Darth Sidious/Chancellor Palpatine. Dooku was the only Separatist aware of his master's true plan and its scope, excluding one minor detail: Sidious had no intention of Tyranus being his final apprentice, and so the Count was beheaded by his soon-to-be successor, Anakin Skywalker.
3 General Grievous
A Kaleesh warlord who aspired to fight like the Jedi, Grievous was turned away by them for lack of capability with the Force. Spurned, Grievous turned to Dooku, who outfitted Grievous with a new, cybernetic body, and placed him in command of the droid army. Trained in Lightsaber combat by his new master, Grievous took great pleasure from killing Jedi, children included. He would take the Lightsabers of any he slew as trophies for his ever-growing collection. His ire wasn't reserved for the Jedi however; at Dooku's direction, he led his droid armies to Dathomir where he committed outright genocide against the inhabitants. A vile being, Grievous would meet his end at the hands of Obi-Wan Kenobi, but considering the pain Grievous inflicted, it came too late.
2 Nute Gunray
If the word "slimy" were to manifest in physical being, it would be in the form of Trade Federation Viceroy Nute Gunray. A penny-pinching coward who made no illusions otherwise, Gunray fell under the sway of Darth Sidious, leading a brutal occupation of Naboo at the Sith Lord's expense. Escaping justice thanks to his massive fortune, Gunray would later throw his lot in with the Separatists, offering the Trade Federation's vast resources to the effort against the Republic. Gunray had an ulterior motive; revenge against former Naboo Queen Padmé Amidala, who had brought him to justice. Gunray thankfully wouldn't live to see his vengeance carried out, however, for he was slaughtered by Darth Vader alongside the rest of the Separatist council, the last of their number to fall. True to form, he went out pleading for mercy where there was none to be found.
1 Wat Tambor
The head of the Techno Union, the corporation which designed most of the Separatists' weapons and battle droids, Wat Tambor took the principle of "profits over people" to its cruelest extreme. Leading a savage occupation of Twi'lek homeworld Ryloth during the first year of the Clone Wars, Tambor ordered the planet's inhabitants to be used as human shields against Republic forces sent to liberate the planet. Captured only because he overstayed his allotted time in plundering the planet of its resources and valuables, Tambor soon escaped and resumed leadership of his company. His next major contribution to the war effort was just as vile. He experimented on the POW Echo, and transformed the clone into a living computer who could project Republic strategies at the Separatists' behest. When Echo was rescued, Tambor explicitly referred to the captive Clone as "Techno Union property" and fretted not at the disadvantage dealt to the Separatist war effort, but his own profit margin. Like the rest of his ilk, Tambor was killed by Darth Vader on Mustafar; he was notably seen cowering at the sight of the Sith Lord, unprepared now that karma had finally caught up with him.