The reunion of Tom Welling and Michael Rosenbaum in the podcast "Talk Ville" is the most exciting thing to happen to the Smallville fandom since Welling returned to screens in the Arrowverse's Crisis on Infinite Earths arc. The former co-stars are working their way through each episode of the classic Superman series, sharing behind-the-scenes information and their perspectives on the show as it developed.
Of course, it brings up familiar arguments such as whether or not Rosenbaum's Luthor is the best version of the character. While that is a subjective question, he is certainly one of the best, bringing new depth to the villain with each new plot twist. Often, this works so well because audiences are comparing the character with who he is destined to become, gradually becoming more canon-compliant as the show went on. Sadly, the same can't be said for every DC villain the show brought to life, with many bearing only the slightest resemblances to their comic book counterparts.
Doomsday
Season 8
Is it fair to call a character Doomsday only to fundamentally change his origin story and abilities? Smallville's take on Doomsday was the genetically engineered son of Zod, rather than a prehistoric, multi-thousand-year-old being from Krypton. Both characters could sense Kryptonians and had a compulsive desire to kill Superman, but other than that, they were entirely different characters.
The version played by Dario Delacio was simply a pawn of Brainiac, which is an unfortunate take on the character that canonically killed Superman. He ended up being a merger of Jekyll & Hyde and Dexter, which was a serious let-down for fans looking to see Clark pitted against a serious threat.
Mister Mxyzptlk
Season 4
Mr. Mxyzptlk dates back to the Golden Age of comics, and while his morality varies across that time, his general being tends to stay the same. Smallville ignored all of this and used the name for a completely different character. Rather than the 5th-dimensional trickster fans know and love, Mikhail Mxyzptlk was a metahuman from the Balkans with some degree of probability manipulation and mind control.
While there were a few minor references to the comics, the two characters are almost entirely distinct. Lex acquiring custody of Mxyzptlk teased a future confrontation where he might be more in line with his comic counterpart, but that plot thread was never returned to. Thankfully, he was considerably better handled in some of Supergirl's best filler episodes.
Brainiac
Seasons 5, 7, 8
Smallville's version of Brainiac, played by Buffy the Vampire Slayer's James Marsters, has a history very distinct from the character in the comic. In the show, Brainiac began as a Kryptonian AI system that was corrupted by Zod and used the name Milton Fine as a secret identity. He has a few different comic origins, alternately originating from the planet Bryak or Colu, but all are very different from that.
Seemingly, the only similarities between the comics and Smallville characters are his intelligence and his connection with the futuristic superhero Brainiac 5. The character certainly shouldn't be Kryptonian and doesn't even shrink any cities, which was his most iconic tendency in the comics. Marsters' portrayal was engaging, but he just didn't feel like Brainiac.
Lionel Luthor
Seasons 1-7, 10
With how significant Lionel Luthor was in Smallville, it might surprise fans to know that the character barely had a role in the comics before the show. Lex Luthor's father was first mentioned in 1961, but he was never a significant figure. The name "Lionel Luthor" didn't even become a mainstay in comics until after Smallville cemented it in the public mind.
The show needed Lex to remain sympathetic for a few years, so they pushed many of his plotlines onto his father. The reveal that Lionel killed his parents for insurance money in "Shattered" is a Lex Luthor plotline from the Post-Crisis era. With all of that said, the biggest deviation from the comics is simply that Lionel Luthor mattered at all.
Darkseid
Season 10
Darkseid is canonically a universe-ending force when he puts his mind to it, so Smallville had to seriously de-power him to face Clark. In the comics, Darkseid's primary goal was acquiring and understanding the Anti-Life Equation enough to get rid of all free will. His goals in Smallville were significantly less threatening.
While Smallville gave Darkseid very little backstory, not having the time to give all the details about Apokolips, New Genesis, and the Anti-Life Equations, Darkseid didn't feel fundamentally wrong. He was just weak. His minions were important players, but Darkseid wasn't, letting down fans who wanted to see Clark face a major threat.
Parasite
Season 8
The Rudy Jones version of Parasite was a serious threat in the comics, but he's more of a freak of the week in Smallville, which limited how much audiences know about him. There's hardly any discussion of his origins, though they could have been an interesting lead-in to Darkseid's arrival. However, the vagueness doesn't make him inaccurate, just underdeveloped.
The version of Parasite played by Brendan Fletcher only really had power absorptions, which made him far weaker than his comic counterpart. Fletcher did a great job with what he had, but the character barely had enough substance for fans to remember him, a shame for such an interesting character in the comics.
Toyman
Seasons 8-10
The Toyman as a character is only a few years younger than Superman, so it only made sense that he would be brought into Smallville. However, the show made the baffling decision to make him more of a Green Arrow villain than a Superman one, which veered pretty far from his role in the comics.
Frankly, it's easier to say what is similar than it is to list the many differences. The show kept the name and the gimmick, as well as having Toyman make a robot version of himself, but that's about it. Even so, most fans enjoyed Smallville's interpretation, which likely led to the importance of Winslow Schott Jr. in Supergirl.
Zod
Seasons 5-10
Thanks to his virtual disappearance from comics after Crisis on Infinite Earths, Zod has been one of the most consistent characters in Superman comics. The version of Zod in Smallville, like the version introduced in Adventure Comics #283, was a military leader on Krypton who rebelled against the government and was sentenced to a prison term in the Phantom Zone.
However, Smallville also had Zod be partially responsible for Krypton's destruction, after previously maintaining a close friendship with Jor-El. These changes made Zod and Jor-El parallel Lex and Clark, which was pretty effective given Zod briefly controlled Lex's body. Smallville's Zod was ruthless, as Zod should be, but the multiple versions of the character occasionally made it difficult for fans to fully connect with the character.
Lex Luthor
Seasons 1-7
Because Smallville is effectively a prequel, they were able to make Lex a compelling and understandable character, so long as he became his comic persona by the end—which he did. Lex's business ventures connect with his depiction in John Byrne's The Man of Steel, his many experiments went back to his earliest depictions, and his political aims tie back to Lex 2000 #1.
Lex Luthor first appeared in Action Comics #23 in April 1940, but his characterization and origins have had so many alterations since that Smallville had to piece different versions together. Silver Age Lex worshiped Superboy—which connects with their friendship in the series—and the Post-Crisis version suffered from the same abuse as Michael Rosenbaum's version did, which gave a good grounding for Smallville's portrayal.
Metallo
Seasons 9,10
Metallo is the most comic-accurate Superman villain in Smallville. Like in the comics, John Corben was a journalist, though he didn't seem to have any criminal tendencies before his accident. The accident itself lined up with John Byrne's reboot in 1986, and the idea of a fellow Superman villain transforming him into Metallo ended up closely paralleling Superman: Secret Origin, which was released at nearly the same time.
As played by Brian Austin Green, the character was very similar to his comic counterpart, from his modes of attack to his obsession with Lois Lane. Even the changes, which largely involve giving Corben a more sympathetic reason for hating Superman, were largely appreciated, as they made him more engaging. Altogether, the visuals, characterizations, and fight scenes were impressive in portraying and elevating the classic villain.