The Avengers: In Operation: Galactic Storm, the Supreme Intelligence completely masterminds things to get the Shi'ar to hit its own race with a Nega-Bomb in order to reignite the Kree's evolutionary cycle, even though it means killing most of the race. When the team finds out one half led by Iron Man attempts to kill it for causing the genocide, and they seemingly succeed... only for the very last page to reveal that it saw their actions coming a mile away and faked its own death, leaving it free while everyone presumes it to be destroyed.
Avengers Arena: Zig-Zagged, as Not-So-Harmless Villain Arcade managed to succeed in getting several young heroes killed off, escaped punishment, and uploaded what really happened on Murderworld to immortalize himself as a true villain while leaving the survivors broken and jaded. However the follow-up series, Avengers Undercover reveals that Arcade didn't exactly find the cred he was looking for after all, as it turns out many of the villains are disgusted by the fact he was only able to hurt children. And then the survivors came calling...
Daredevil: Mister Fear in the "To The Devil, His Due" and "Without Fear" arcs. Not only does he does cause irreparable damage to the hero's life, but his powers only make life in prison a veritable paradise that he can leave at his leisure to once again torment the hero.
Fantastic Four: Doctor Doom with, well...◊ While some could say this story did have a happy ending with Doom cooperating with the Fantastic Four for mutual benefit (Valeria was born unharmed, as Doom was able to prevent Sue's miscarriage that "killed" her the first time, likely saving Sue as well) Doom's benefit was greater, and possibly his greatest victory to date in his feud with Reed. He was able to tell Reed to his face, with absolute truth, that he had succeeded where his rival had failed.
In a more traditional sense, Doctor Doom has on more than one occasion succeeded at plots to Take Over the World and defend his dictatorship successfully against heroic rebellion, eventually yielding his position out of sheer boredom.
The Infinity Gauntlet: For most of the story this is the case where everyone who attempts to take on Thanos ends up get beaten by him including the most powerful cosmic beings. Then zigzagged when Thanos is finally defeated, but it is revealed that he let himself lose because deep down he feels he does not deserve to win]].
Marvel Two-in-One: Annual #7 featured the alien Champion of the Universe defeating all of the heroes that trained to fight him, but he ended up sparing the Earth because he found Ben Grimm (aka the Thing) to be a worthy opponent.
The Mighty Thor: In Journey into Mystery (Gillen) Kid Loki manages to save the day against all odds. But his true Arch-Enemy Old Loki has trapped him in a situation forcing him to choose between letting Mephisto run amuck as the new king of Hell with the Fear Crown Kid Loki created or saving all of reality by destroying the Fear Crown which can only be done if Kid Loki allows Old Loki's memories to overwrite his own, completely erasing Kid Loki from existence. Kid Loki chooses the latter, though he takes one last parting shot at Old Loki, calling him out on his Chronic Villainy.
The Clone Saga ends with Spider-Man's clone, Ben Reilly, who Spider-Man has come to regard as a brother, being impaled by Spider-Man's nemesis Norman Osborn. Norman had previously killed Peter's girlfriend Gwen Stacy. Ben's last words to Peter are to remind Peter's daughter of her uncle Ben. Of course this is a moot point since Norman already had Mary Jane poisoned and she presumably lost the baby. Ben didn't know that though.
The Vulture (Adrian Toomes) has had an astonishingly high success rate in accomplishing various goals over his career:
Willed himself to health to defeat an usurper who tried to kill him in prison? Check.
Eventually killing the man who betrayed/ruined him financially? Check.
Get a horrific revenge on the white supremacist thug who threatened his family and forced him to build the thug a flying harness to escape from prison? Check.
Doctor Octopus essentially won the long game by taking over his body and starting Superior Spider Man...and to make sure, he made Peter Deader than Dead by erasing his brain waves in issue 9. But some would say he suffered the greatest loss of all in the end, when he realized he was a failure who had caused more disasters than he ever could have prevented, and restored Peter, deleting himself from existence.
Ultimate Comics Thor: Loki betrays Asgard and leads the Frost Giants and a full Nazi army (with machine guns, tanks and modern military hardware) against it. Asgard is destroyed, and everybody dies.
Venom: In Venom (2003), despite the best efforts of the Suit, Trish, and the Fantastic Four, the first stage of Bob's plan comes to fruition when Venom assimilates the symbiote clone and decides to follow its directive.
◊ While some could say this story did have a happy ending with Doom cooperating with the Fantastic Four for mutual benefit (Valeria was born unharmed, as Doom was able to prevent Sue's miscarriage that "killed" her the first time, likely saving Sue as well) Doom's benefit was greater, and possibly his greatest victory to date in his feud with Reed. He was able to tell Reed to his face, with absolute truth, that he had succeeded where his rival had failed.
