The Mass Effect sci-fi trilogy certainly has no shortage of powerful, compelling, and memorable villains, some of which are people with a cunning agenda while others are horrors on a cosmic scale. It's up to Commander Shepard of the Alliance Navy to face these threats and find victory, or else all will be lost.
What are Mass Effect's villains after? Some of them are driven by vengeance or grief, while others seek retribution or are simply acting in their nature. Some are merely pawns and unwitting victims, such as Matriarch Benezia, and others are merely acting by instinct, such as the massive Thorian on Feros. Other villains, however, are either impossible to root for or went too far to earn forgiveness.
10 Saren Arterius, Sovereign's Turian Puppet
As a whole, Saren Arterius is not easily forgiven, and both paragon and renegade Shepard will urge him to take his own life to break away from Sovereign (and neither will grieve for Saren). It can be said in Saren's defense that he was indoctrinated, and he honestly believed that he was building a more peaceful future for everyone. He wasn't 100% evil.
However, Saren went too far to earn major sympathy from Shepard or the player. Before becoming indoctrinated, Saren was viciously anti-human, and he sabotaged David Anderson's attempt to become a human Spectre. Saren also tortured and coldly executed many innocent or semi-innocent people during Spectre missions.
9 Tela Vasir, A Ruthless Asari Spectre
Like Saren, Tela Vasir had a shred of goodness to her, though she crossed some serious lines during her tenure as a Spectre. Tela Vasir thought that even her fellow Spectres didn't go far enough to fight terrorists and criminals, so she allied with the notorious Shadow Broker.
Vasir became a borderline terrorist herself to take down criminals all over the galaxy, and she didn't mind sacrificing civilians to get the job done, much like Saren. However, Vasir's rampage came to an end when she tangled with Shepard and Liara T'Soni on Ilium.
8 The Illusive Man, Cerberus' Big Boss
The Illusive Man is one of the few Mass Effect villains who has at least a shred of virtue to him, to balance with his cruel and ruthless actions and rhetoric. The enigmatic Illusive Man genuinely wants to look out for the vulnerable humanity in a sea of sharks, which is understandable, but he crossed one line after another to do it.
Even before Cerberus allied with the Reapers, The Illusive Man and his minions acted as borderline terrorists and mad scientists, and the Illusive Man wrongly thought that stealing Collector/Reaper tech would unlock the future. He jeopardized humanity's real future to seize that power, and thus, he had to be stopped. Not even renegade Shepard can sympathize with that.
7 The Collector General, Harbinger's Favorite Pawn
The Collector general's only sympathetic element is the fact that it, along with all other Collectors, is a Prothean husk. The Collectors are a synthetic race of sorts, now serving the Reapers that made them, and the Collector General coordinates the efforts of Collectors everywhere.
Otherwise, though, there is nothing to appreciate about the Collector General, who is Harbinger's unthinking pawn, an ice-cold killer. There is zero chance for the General's redemption or freedom, and the General is Shepard's mortal enemy. In fact, Paragon Shepard will vaporize the Collector General and their base with a powerful explosive device.
6 Balak, A Batarian Terrorist Ringleader
The Batarian people came into conflict with humanity when the Alliance unwittingly moved into Batarian frontier space to set up colonies, and the Council did nothing to aid the Batarians. Ever since, the Batarian Hegemony and Alliance have been enemies, and Batarian pirates and slavers regularly terrorize human colonies and ships.
Balak, in particular, is determined to see humanity suffer, but this will do little, if anything, to better the lives of other Batarians. Instead, he is committing acts of terror out of sheer anger and spite, and there is no forgiving that. He has every reason to lament the current state of Batarian affairs, but this is going way too far. Just look at the Asteroid X-57 incident of 2183.
5 General Oleg Petrovsky, Who Challenged Aria T'Loak On Omega
General Oleg Petrovsky is a classic smug villain, the type who fancies himself some noble aristocrat-general, complete with expensive drinks, classic quotes, and chess analogies. In the year 2186, Oleg allied himself with Aria T'Loak, then betrayed her and conquered the outlaw space station Omega.
Oleg was ruthless, and he set up terrifying synthetic soldiers and energy barriers to keep the people of Omega in line, and he tried using psychological warfare on his enemies on top of that. Once defeated, the slippery Oleg tried to talk Shepard and Aria into taking him prisoner, despite all he's done, but if Shepard doesn't interfere, then Aria will strangle him.
4 Kai Leng, The Illusive Man's New #1 Minion
For a time, Miranda Lawson was practically The Illusive Man's top agent, but when Miranda quit Cerberus in 2185, this left the assassin Kai Leng as the #1 Cerberus operative. Kai Leng had once been in the Alliance military, but he had been brutal and lacked restraint or honor. He racked up many infractions there.
Now, Kai Leng is The Illusive Man's weapon of choice, coldly and ruthlessly carrying out deadly missions all over the galaxy. Kai Leng killed Thane Krios and nearly killed the Salarian councilor, and he swiped the Catalyst from Shepard on Thessia as that world fell to the Reapers. It was a satisfying renegade interrupt when Shepard killed him at last.
3 Henry Lawson, Who Sought To Build A Personal Dynasty
Miranda Lawson's "father" is Henry Lawson, a wealthy and extremely self-centered businessman with strong ties to the Cerberus organization. Henry isn't trying to conquer the universe, though; instead, he aims to create an immortal dynasty through his genetically engineered daughters, Miranda and Oriana.
Henry made no apologies for his selfish ambitions and his merciless ways, and he died stubbornly fighting Shepard and Miranda on Sanctuary. He even took Oriana hostage, something Miranda could never forgive.
2 The Shadow Broker, Pulling All The Strings
Everyone knows what the Shadow Broker is, but not who the Shadow Broker is. This mysterious agent will charge stiff fees in exchange for sharing secrets and vital intel to any interested party often business leaders, military commanders, and politicians. Everyone is fair game in the Broker's eyes as potential clients or victims.
The Shadow Broker is a brutal and thorough alien, using any means whatsoever to get what he wants. The Broker tried to sell Shepard's dead body to the Collectors, and the Broker is willing to sacrifice his agents and cause serious collateral damage during operations. Shepard and Liara finally disposed of him in 2185 once a Salarian named Sekat zeroed in on his location.
1 Sovereign, The Vanguard Of Everyone's Destruction
Strictly speaking, the terrifying Reaper named Sovereign is just doing its job as intended, but that does not excuse anything Sovereign has said or done. This mammoth Reaper capital ship routinely indoctrinates, uses, and discards many followers, with Saren being a prominent (but not the only) example.
Sovereign is not even alive, but rather, is an organic/machine hybrid that is impossible to personally relate to in any sense. This cosmic monster has no emotions or sentiment of any kind, merely carrying out its duty over millions of years to ensure the extinction of yet another advanced civilization in the galaxy.