Warning: Spoilers Off applies to this page. Proceed at your own risk.
The second episode of the anime opens with a funeral for the protagonist's parents. One he had skipped in favor of masturbating to footage of his niece. His relatives come home and upon discovering this, immediately throw him out.
Rudeus was absolutely miserable in his first life. He wanted to live a full life but his phobia was so bad that he couldn't bring himself to leave the room; all he could do was watch as everyone else left him behind. Every hobby he pursued, every kink he developed, was all part of a desperate attempt to drown out his growing despair.
Rudeus remembers a time when, after throwing a tantrum, he brooded in his room while his brother simply sat there quietly. The two of them wanted to reach out to each other, one to help and the other to be helped, but they couldn't figure out how to bridge the gap between them. In the end that gap would just grow larger and larger until the funeral, by which point the protagonist had so thoroughly alienated himself from the family that he truly believed his parents no longer loved him.
The Mana Catastrophe—What could've been inclined as at least some sort of Slice of Lifeisekai story with serious moments up to this point dives right off of a cliff, as Rudeus' entire life is uprooted, his home village is gone and his family scattered to the winds due to the incident teleporting people all across the world. It irrevocably changes the lives of the entire cast and kickstarts many personal, familial, political, and even global problems that would haunt everyone for the rest of the series. Indeed, it straight-up kills most of the people involved in it, as you'd expect from a spell that teleports each person in a huge radius to random locations in the world without warning, including high in the air, where you'd promptly fall to your death. Even the ones lucky enough to survive both the initial teleport and being lost and alone in random parts of the world end up as refugees.
The horrific event when Rudeus gets internally-shocked of what he witnesses as he's retrieving Ruijierd after a shady individual smuggles him on the ship so that they could avoid paying the absurd fee they'd be forced to do otherwise is nothing short of heart-rending sorrow. Rudeus bearing witness to a poor demi-human child◊ literally wanting to escape from her wretched fate as she attempts to reach for Rudeus beyond the bars just hits you like a emotional jackhammer, especially as Ruijierd mentions she dies (as if the auditory clue wasn't clear enough) shortly after her slave-handler punishes her earlier act lethally, further demonstrating that things can always get worse for unfortunate souls like them...
Rudeus' eventual reunion with Paul after spending a year and a half trying to make his way through the Demon Continent is heartbreaking. Rudeus decides to embellish on his journey, playing it up as a "fun adventure" because that is what he expected Paul would want to hear based on how their relationship was in the past. Unbeknownst to Rudeus, Paul had spent the entire time running himself ragged trying to find his splintered family, drinking himself into depression. Paul even tried to send communication to Rudeus via the Adventurers Guild, but Rudeus was so laser-focused on making it he didn't even think about considering that. This results in both parties slinging a "The Reason You Suck" Speech at each other, Paul calling out Rudeus for treating the situation as a joke and not carrying enough about their family, while Rudeus throws Paul's infidelities into his family. This ends up devolving into an actual fight.
The next day when the two finally do have a sit down to talk everything out, Rudeus thinks back to his previous life and it gets revealed that he actually did have a friend who cared about him throughout everything he went through. They had a falling out after Rudeus lashed out and attacked his friend over a joke, ultimately driving him away. And rather than apologize, Rudeus remained in his room because he was too scared to face him again.
Episode 22 hits you with one moment after another.
Rudeus finally makes it back to his family home in Buena Village, only to find it destroyed and empty. The ghosts of his memories playing as he walks through the ruins of his childhood home makes it all the more bitter. The landscape is desolate and even the tree he and Sylphy hung out under is dead. The constant between the present and the green land it once was is painful. You Can't Go Home Again, indeed.
And then having fulfilled his promise, Ruijerd must depart. He gives his farewells to both Rudeus and Eris, with Eris left sobbing. Then Ruijerd departs on his way, promising that they will meet again.
Eris arrives in the ruins of Fittoa to learn all of her family are dead. She calmly tells everyone to Get Out!, before she breaks down crying.
Rudeus waking after his and Eris’s first time to find her gone with only a short note left behind.
Rudeus and Eris feeling they're not good enough for each other and the resulting Poor Communication Kills, particularly the latter's monologue. Doubles as heartwarming given how much she loves him and how he's helped her grow.
Eris: "I love Rudeus. I've loved him since we were young. And my love only strengthened after the teleportation incident. [...] But I realized then, just how small his hand was. I remembered that he was actually younger than me. And I'd just been taking advantage of him all that time. [...] I love Rudeus. And that's why I need to distance myself from him. [...] I'll become so strong, so next we meet, let's become a family for real. I love you, Rudeus."
When Rudeus was Drowning His Sorrows after Sara belittled him for not getting it up, Soldat shows up and starts making fun of him now that his Stepford Smiler persona is cracking. Rudeus snaps and punches him in the face, and keeps punching him while shouting out his own grievances (and his self-loathing and abandonment issues), all the while Soldat not saying anything and defending himself.
Rudeus: What's wrong with smiling whenever I want, huh?! Maybe I should go around insulting and belittling people just like you! If I could get away with that shit— if I could stand to make everyone around me resent me— if I didn't care whether I drove everyone away from me— if I could keep your attitude without hating myself, then yeah, maybe I would! I don't want anyone to hate me! That's why I'm always smiling like that! What about that pisses you off so much?! (sobbing) I just want you to stay. Smile even if you don't even mean it. It's not that hard, and it hurts when you're so cruel to me! (stops punching, dejected) Whatever, I'm done. I don't care anymore. So bring it on. Hate me, dammit, and have your fucking fun. Then when I'm sprawled down you can look down on me and laugh. I know I can't take you in a fight...
When Nanahoshi carelessly says that she caused the teleportation incident, Sylphy snaps and starts attacking her, screaming about all the lives lost because of the incident, including those of her own parents. When Rudy tries to stop Sylphy, she becomes confused and asks him why he's defending Nanahoshi since she knows he also suffered during the years following the incident. Sylphy only calms down and apologizes once Rudy clarifies that Nanahoshi was as much of a victim since she wasn't summoned willingly, but by then it's clear that, even if Sylphy was lucky enough to endure and survive, the pain from the last five years is still there.
Sylphy: IT WAS YOU?! EVERYTHING I— WE WENT THROUGH! MY MOM AND DAD! ALL BECAUSE OF YOU! Rudy: Calm down! Sylphy: WHY?! SHE JUST SAID SHE CAUSED IT ALL! HOW CAN YOU BE SO CALM?! I KNOW... I KNOW THAT YOU SUFFERED, TOO!
Nanahoshi, as someone from Earth having found themselves transported to the Six-Faced World by circumstances utterly beyond their control, has spent the better part of the last five years constantly searching for a way back home all while essentially locked in stasis, with her being deprived of the ability to age normally. Upon learning the truth of Rudeus' origins, she believes she's finally found a kindred spirit and someone talented enough in magic to help her discover the missing piece of the puzzle that will send her back, but even that is not enough to stop a failure that sends her careening over the edge. After a fruitless experiment, the culmination of a solid month of preparation and all the research she has conducted across the years, she simply sighs in utter defeat and flatly tells Rudeus to go home. It takes all of a few seconds of Rudeus being out of earshot for her to start violently destroying her workshop, screaming out her desperation in overflowing anguish before descending into near-total catatonia, convinced that no matter what she tries, she is doomed to remain in a world not her own.
Nanahoshi: I can't go home! I can't go home!I CAN'T GO HOME!I CAN'T GO HOME!
◊ literally wanting to escape from her wretched fate as she attempts to reach for Rudeus beyond the bars just hits you like a emotional jackhammer, especially as Ruijierd mentions she dies (as if the auditory clue wasn't clear enough) shortly after her slave-handler punishes her earlier act lethally, further demonstrating that things can always get worse for unfortunate souls like them...
