At the end of Joss Whedon's run on Astonishing X-Men, the X-Men managed to save the world from a large bullet that was sent by the citizens of the Breakworld, but Kitty Pryde ends up being stuck in the bullet after phasing it to make it pass through the Earth and ends up spiraling out towards space. The second-to-last panels had Colossus looking up at the sky in sadness.
The final issue of the 2009-2011 Batgirl series ends with a montage of stories that the writer had planned to tell, including a team-up between Batgirl and her friend Cassandra Cain (whose absence had been a frequent criticism of the book) and a sword-and-sorcery adventure with Supergirl and Miss Martian. Despite the deliberately sad What Could Have Been montage, the book ends with Batgirl noting that the story would never end as long as the fans continued to remember it.
Before Watchmen: Minutemen ends with Silhouette, Gretchen, and Dollar Bill dead, Byron Lewis confined to a mental hospital, and Hollis Mason spending the rest of his life being blackmailed by the Comedian after the latter tricks him into killing Hooded Justice by framing HJ for the "Friend of the Children" murders. On the other hand, Mason has a goddaughter to dote upon and a successor to train, and a job that he loves. Meanwhile, Nelson Gardner is in a presumably healthier relationship.
Every ending in the Blacksad series is bittersweet. Blacksad finds the missing girl, but her mother is now dead. In another album Blacksad stops nuclear proliferation but doing so loses him the woman he had come to love.
Warhammer40000 comic Bloodquest, the quest to recover the Blood Angels' relic sword is successful and the heroes managed to stop a Black Crusade from rampaging across the galaxy, but all members of the group are dead save for a single survivor, and the leader who sacrificed himself to end the crusade was previously possessed by a Daemon. Even the Sole Survivor's escape is uncertain since he is last seen drifting in space waiting to be picked up by a Imperial vessel.
The ending of Bone is quite bittersweet. The Lord of Locusts is destroyed, Kingdok and Briar are killed, Thorn becomes queen, the Valley is at peace, and Fone Bone makes peace with the two Stupid Rat Creatures. But Lucius is dead, Fone Bone and Thorn will probably never see each other again, and the Bone cousins have to leave the valley forever. The last scene has the Bone cousins and Bartelby heading out into the desert together, planning to return to Boneville...
At the ending of Circles, Paulie sadly dies from leukemia and Douglas finds it hard to cope. Until he realizes that he still has family who loves him and takes care of him. Paulie did what he could to keep the family together and on good terms so that they are never alone after his passing.
Crimson ended with Lisseth being defeated and her apocalypse prevented. However, untold innocents perished during the dragon attacks around the world and two of the hero's companions (one of them being his love interest) pulled a Heroic Sacrifice during the final battle. The hero remained a vampire at the end after fulfilling his purpose, so he is forced to leave his loved ones behind (his father becomes a US senator, while his other love interest joins a convent) so he can embark on a new quest to become human again and return to them.
In Deep Gravity, the planet Poseidon is toxic to humans who stay too long, and personnel are therefore rotated through it rather than permanently stationed there. The freighter Vanguard is conducting one of these rotations, and when it's destroyed, a few survivors escape down to the planet. Most are newcomers, but one of the survivors is Michelle, who was among the group who had already had their maximum safe exposure and needed to leave. It's left open whether or not Poseidon's slow poisoning will prove fatal before another ship arrives, but it doesn't look good.
The short-lived X-Men spinoff comic District X has such an ending. It features the POV character, Officer Ismael Oetega, managing to rebuilt his shattered family life; however, this comes at the cost of his daughter's life and the mutant gifts of almost everyone in Mutant Town. Also, a recurring character stayed in one place too long and turned into a tree.
In Elseworld's Finest: Supergirl & Batgirl, Lex Luthor's crimes have been exposed, his relationship with the Justice Society has been ruined and his worst enemies -Supergirl and Batgirl- are now friends and allies. However, Superman is dead, the parents of Barbara are dead and unavenged yet, and Luthor will buy his way out of jail.
In the Marvel Graphic Novel Emperor Doom, the Avengers are able defeat Doom and get him to restore humanity's free will, but in doing so, everything is restored to the status quo, which we're shown as the Russians march back to Kabul, Afghanistan, Apartheid being restored in South Africa (with a hotel owner being shocked that he could let "colored" people in), and a cigar-chomping US General demanding their nukes be rearmed once more. This makes Hawkeye wonder if they've done the right thing.
The ending of Final Crisis sees Darkseid and Mandrakk defeated, and Superman using the Miracle Machine to restore space/time to its normal state. However despite Nix Uotan's claim that Superman wished for a happy ending with the Machine, that is not the case. Because the Machine could only be used once, the deaths of the Anti-Life-enslaved people and both Batman and Martian Manhunter still happen. Superman could have helped out earlier, if only he had returned from the 30th century earlier.
A God Somewhere: Superhero-turned-megalomaniac Eric Forster has been defeated, but he went on a rampage of death and destruction across the U.S. before he was put down. And the friends he left behind continue to be negatively affected by his actions; Alma, who was raped by Eric, suffers from PTSD while Sam abandons his journalism career.
At the end of Kingdom Come, the heroes have all made peace with each other, done away with secret identities, regained the world's love and trust, and last but not least, Superman and Wonder Woman are married and having a child. However, many of the heroes were killed during the climax by a nuclear explosion.
The Livewires mini-series ends with all but two members of the team of Ridiculously Human Robots damaged possibly beyond repair. The least damaged and most recently activated, having saved the rest, tries to take them to their original base for supplies, only to discover the team blew it up before the start of the mini series.
In Many Happy Returns, Kara and Linda manage to save New Earth -the Post-Crisis universe-. However, Linda has to leave her husband and daughter behind and send Kara back to her universe and eventual death. As a result of it, she hates herself for being unable to protect them, and retires. It became a bit less bitter after Pre-Crisis Kara's death was undone during Convergence.
In Mass Effect Redemption, Liara manages to recover Shepard's body, but her friend Feron is captured. Liara then gives Shepard's body to Cerberus in the hopes that Cerberus can revive Shepard. Liara's not entirely convinced that she did the right thing.
My Little Pony Micro Series #3: Rarity is of course upset at high society paying attention to her hippie friends and ignoring her, but she consoles herself at least her new friends are happy and have given her a lifetime supply of their product in gratitude of her help while Twilight points out that her own fashion show was a big success itself with a slew of new commissions for her business.
The end of the DC event Our Worlds at War sees the world mourning the apparent deaths of Aquaman, Guy Gardner, Sgt. Rock, and Hippolyta, with Superman himself mourning the destruction of his family farm and apparent deaths of the Kents, along with the rest of the state of Kansas.
At the end of Joann Sfar and Emmanuel Gilbert's book The Professors Daughter, Ihmotep and Lillian get married and have three children, but Lillian's father is killed and wrapped in bandages, and then placed as a part of the Museum's Egyptology exhibit.
The Sandman: "The King Of Dreams is dead. Long live the King Of Dreams."
Sin City stories often end with the hero defeating and possibly even killing the Big Bad but at the cost of his life... one way or another. Wallace's story Hell and Back is perhaps the only 100% happy ending in the entire series.
The ending of Sonic the Hedgehog/Mega Man: Worlds Collide is this: Mega Man's able to restore his world to how it was, but Dr. Eggman, refusing to let Sonic win, interrupts his Chaos Control, then attacks it, transforming Mobius to a version never seen before. A few issues later, we learn that it did worse than that: the entire multiverse collapsed upon itself and then rebuilt then, Mobius shattered.
Spider-Man: Noir: Eyes Without a Face ends with the Crime Master dead and Dr. Octavius being rejected by his idol Heinrich Himmler as a "deviant cripple." But Robbie Robertson has permanent brain damage from Octavius' experiments, Felicia Hardy has become a heavily scarred shut-in who never wants to see Peter again, and the Nazis have risen to power in Germany. Almost lampshaded by Peter near the end of the series, when he tells Mary Jane that his life is falling apart - and he thinks it's only going to get worse.
In Marvel Swords of the Swashbucklers comics (spin off of Marvel Graphic Novel of the same name) final issue (#12) Domino Drake (an Earth teen who had been traveling with the alien Swashbucklers) used her elemental powers to fight the Swashbucklers pursuers, the Colonizers. Unfortunately, her flame ignites the Cloudwall (an unstable space abnormality between dimensions). She turns her body to stone to shield her and her cat, Cap’n Kidd, and leap off the ship. As she passes through the Cloudwall back to Earth, the Swashbucklers’ ship disintegrates behind her. She returns to the beach house where her parents and Dodger (a former thief from the Swashbucklers’ dimension) lives. Domino is reunited with her friend and parents but it is unknown if she still have her elemental powers, Cap’n Kidd is no longer sentient, and all of the Swashbucklers are dead.
Transformers: Regeneration One's present-day aftermath of the final issue is very bittersweet. Rodimus Prime has defeated the dark Matrix creature, ending the threat it posed to the multiverse, but at the cost of forever cutting off his own universe from Primus; Optimus Prime has died again, this time for good; thanks to the Matrix creature, Cybertron has been rendered uninhabitable; and most of the Transformer population on Cybertron were turned into shadow-leeches by the creature, before its defeat allowed what was left of their sparks to pass. But, the Distant Finale reveals that the Forever War has come to an end, as Autobots and Decepticons become emissaries of peace; the survivors of Earth and Nebulos succeed in rebuilding their worlds; and eons later, when Rodimus finally passes, his Matrix-spark breathes new life into Cybertron, allowing the long-dormant Primordials to be reborn as a new race.
The Shadowplay arc was a flashback arc dedicated to bringing Rung out of a coma by trying to get him to remember. It has Optimus (then Orion), Ratchet, Windcharger, Skids and one of the few good Senators all coming together to stop a malicious plot by the senate to kill a bunch of innocents and frame the, then innocent, worker's party. It succeeds, they retrieve the bomb, and save everyone. However they can't find any evidence connecting the senate to the bomb spree, the Senator is taken away, and Optimus befriends Zeta, who would grow up to be another tyrant. The arc concludes with Rung waking up in the present while the senator had the titular Shadowplay performed on him, turning him into the emotionless Mad Scientist Shockwave, whose schemes would come to threaten the whole planet.
Season 2 ends with Megatron cementing his Heel–Face Turn by killing the Decepticon Justice Division, the return of several missing Cybertronians like Terminus and Roller, Overlord and Deathsaurus retreating, and Ratchet and Drift rejoining the crew, but it comes at the cost of Skids and Ravage's lives, and the crew are still stranded from the Lost Light thanks to Getaway's mutiny.
Transformers: Wings of Honor: The ending of the second Arc is actually happier than the first.Deathsaurus is defeated and driven back, the traitorous Combaticons are locked away and the autobots succeed. However, so many have died at this point including Ricochet, one of the comic relief characters. In the end, Rumbler is killed in the final battle, and Sprocket, the resident Cloudcuckoolander, continues to talk to him as if he was alive. The Hero, Dion is shot along with The Captain Magnum, both are near death, when they go into operation, one dies, and the other emerges as Ultra Magnus. The Autobots all agree to leave or go into stasis, taking their war away into the Generation one series.
The Dragon Age tie-in Until We Sleep ends with Aurelian Titus defeated and Alistair finally meeting his long-lost father Maric. Unfortunately, Maric is only being kept alive by an ancient magical artifact and Alistair destroys it in order to release his father. Alistair then returns home to rule Ferelden as an unhappy king. Isabela, scarred by her imprisonment at the hands of the qunari, is shown leaving her life as a pirate.
V for Vendetta: V and Evie have triumphed against the evil fascistic government. However, V is dead, chaos runs rampant throughout Britain, and it seems like the last bastion of civilization is crumbling.
War of the Green Lanterns: The Green Lantern Corps is saved, the emotion entities are freed from Krona's control, the New Guardians are freed from the Book of the Black, and Sinestro is a Green Lantern again. However, thanks to Hal Jordan's actions, the Guardians of the Universe find him too dangerous and has him dishonorably discharged from the Corps. The story ends with Hal back on Earth in the middle of nowhere, muttering, "This isn't how it's supposed to end."
Watchmen: Dan and Laurie are happily together and fighting crime and the looming threat of nuclear war has been eliminated, but Ozymandias killed millions of people, Rorschach is dead, and Dr. Manhattan just sort of... left.
We3: 3 doesn't survive the encounter with 4, but 1 and 2 are adopted by the homeless man who tried to help them earlier in the series.
Y: The Last Man ends in a Distant Finale where cloning has been perfected and the first twenty or so reliably immune men have recently been released into the "wild". however Yorick Brown 1.0 himself does not fare quite so well. He finds out that the girlfriend he had rounded the globe tracking down was about to dump him when the fateful telephone call was cut off; eventually she shacks up with his sister. Then the woman that had been slowly falling in love with him, 355, gets shot dead at Alter's command in the hopes of securing an "honorable" death in combat with the only available male. He begins the Distant Finale straitjacketed and locked in a hidden room in the French Presidental Palace by his own daughter after an apparent suicide attempt shortly before his eighty-sixth birthday... he claims he thought it would be ironic.
Though he does escape in the end, and is implied to be alive. His escape might also qualify as a Chekhov's Gun, as he is seen practicing a straitjacket escape in the first issue.
And it's not just Yorick whose life didn't exactly turn out perfect. He and Beth-Two spent years in a loveless marriage that held together solely for their daughter's sake. Ciba was essentially kidnapped to Russia at gunpoint by a woman she thought was her friend so her son could be forced into the role of national savior. And for all her efforts, Dr. Mann died before she could duplicate her father's method of human cloning.