Effectively any time Blackjack breaks down. A Hurting Hero indeed.
The terminal entries left by Granny Smith's boyfriend Hoss, detailing most of the important and personal events of the war, including the deaths of Big Macintosh and Granny Smith. Blackjack and P-21 than bury Hoss' remains in the grave beside Granny Smith.
Consequently, P-21's attempted suicide in Chapter 25.
Blackjack's reunion with Glory in chapter 25. Glory is initially livid with her over her suicide attempt but gradually breaks down and confesses that, without Blackjack, she had nothing left to live for.
Blackjack's tearful reconciliation with P-21 at the end of Chapter 33, and subsequently, her death.
Chapter 43. All of it. Everything from Blackjack's heartbreaking refusal to believe that her friends don't exist outside of her mind to her finally reaching some level of closure with her mom to the abandoned Happyhorn computer slowly trying to comprehend that it can't ever fix her.
Lacunae's death after the destruction of the Goddess. Being a fusion of all the discarded emotions and memories of the ponies fused into Unity, she performs a Heroic Sacrifice and destroys herself to restore the memories of her sisters. Psalm is resurrected as a result, but she is not Lacunae.
Goldenblood and Fluttershy's doomed relationship. During a moment of intimacy, Goldenblood calls out Luna's name (since she decided to have a telepathic chat with him at the wrong moment). This causes Fluttershy to think he is unfaithful, and goes into early labour, and have a miscarriage. Though this obviously turns out to be false since Sanguine saved the baby who became Psychoshy. It only gets worse as revealed during Goldenblood's key memories, he searches Equestria for Fluttershy during the Last Day, saying a heartfelt goodbye to Celestia, Luna, and Rarity. He tracks down Fluttershy who silently watches the megaspells destroy Equestria, the gift she gave to the zebras out of kindness and with a little help from her ex-lover. While Goldenblood tries to apologise, Angel Bunny attacks him, and he is then dragged away to the Underworld, separated from his beloved Fluttershy forever.
Big Mactinosh: Gunned down by Psalm in an attempt to assassinate Princess Celestia, and his death was made to look like a Heroic Sacrifice.
Applesnack: Reassigned to guard Zebratown, became the first Steel Ranger, murdered Zecora, broke up with Applejack, and then became a ghoul.
Twist: Raped by Doof, her zebra lover Shujaa is killed and gives her the Phoenix Talisman, trapping both in it. Twist later becomes part of Rampage.
Psalm: Went from a devoted follower of Luna driven by faith to a self-loathing Cold Sniper. She carried out Project Partypooper, murdered Pinkie Pie, and was then absorbed into the Unity, became Lacunae, and used as a dumping ground by the Goddess for all the unwanted emotions and memories.
Doof: Manipulated by Brass into raping Twist, sent to Hightower Prison, grew to hate all mares, and eventually transformed into Deus through Project Steelpony.
Stonewing: His death was faked by Sanguine so he could be used for Project Chimera and transformed into Gorgon.
Jetstream: Vanity erased her memories and thus love for Stonewing after his "death", then went insane following Big Macintosh's death and put in an asylum.
Vanity: Tried to hold the team together but quit after Jetstream's mental breakdown. Killed by his brother Blueblood for sleeping with Rarity.
Echo: Considers himself a Dirty Coward for standing by and doing nothing as his team fell apart. He eventually was employed by Goldenblood but his soul was attached to EC-1101 to protect it from misuse. Echo became the Dealer and betrayed Blackjack to Cognitum to get back his body.
Marigold's story. Twilight Sparkle's cousin, Marigold earned fame by being the first astropony to land on the moon. But when she returned, she became the surrogate mother unknowingly to Twilight's baby, naming her Tarot. Unfortunately, the press gained wind and she was dragged down by the media for her mysterious pregnancy. She spent the rest of her days living like a hermit, until the Last Day, sending Tarot into Stable #99 to survive. Blackjack comes across her corpse centuries later, holding a photo of Tarot. We also learn Marigold was meant to be in Stable #90, which was doomed from the start thanks to Goldenblood.
Glory breaking up with Blackjack after her return from the Core.
Chapter 71. The whole thing is pretty gloomy, with themes of uncertainty and nopony knowing if the day fighting the Harbingers will be their last. It was clear something terrible was just on the horizon, which just makes the ending so much worse. In accordance with the Anypony Can Die theme, the ending has Glory stay to keep a rocket functional so that Blackjack can stop Cognitum from activating Project Horizons, while the both of them knowing the Legate had launched a Balefire missile with no way to stop it. Glory stays to ensure Blackjack has a chance. If the Balefire didn't kill her, the enemy shrapnel left her bleeding to death. She'd been with us since nearly the beginning, suffering through so much... But now, Glory is dead.
Chapter 74. Echo is devoured by mechasprites, P-21 is Impaled with Extreme Prejudice and has to be left behind in the collapsing Lunar Astrostable. Then a page later, Rampage is shown unable to leave too, forced to hold up a mountain of metal or P-21 dies. The terminal P-21 is trying to use causes the whole place to explode, Scotch Tape offers to stay behind so Blackjack can escape, then Rampage pulls a Heroic Sacrifice to get her friends to the escape rocket whilst being directly exposed to the vacuum of space and is left to wander on the Moon's surface. Blackjack plays the Johnny Cash song "Hurt", remembering her friends and wanting to stay together with them.
Chapter 75's two parters are mostly this, featuring Blackjack using the Perceptitron to keep an eye on her numerous allies battling for Hoofington, but each new location swap shows more and more tragedy as numerous supporting characters die. Amongst them are Big Daddy, Harpica, Silver Spoon, Rainbow Dash, Deus, Sekashi, and Goldenblood.
Chapter 76 opens with Glory's confirmed survival, only for her to die several pages later in Blackjack's arms. Blackjack is then dropped off at Star House by Spike, where she sits alone remembering everyone who died because of her to the song "Empty Chairs, Empty Tables", and then lets out a Skyward Scream til Boo gives her a Cooldown Hug.
The long-awaited epilogue. It is a Bittersweet Ending to say the least.. Scotch Tape went to the zebra homelands to rescue their sanitary facilities, Fluttershy and Whisper finally meet, and most surviving characters have happy endings. Four-hundred years on, Blackjack, Littlepip, and Boo are all immortal, Celestia's soul is gone, Spike is a cynical hermit due to a war with radioactive undead dragons, and Boo has become the Discord-esque Mare Do Well who bombs people to keep order in Equestria. Blackjack and Littlepip finally make it to the moon, where they find Rampage has died. However, when Blackjack destroys the Phoenix Talisman, Peppermint is resurrected as a filly, finally allowed to live a normal life.