I have a few to talk about, but I'll try to hide 'em in spoiler tags for each series.
Attack on Titan (anime and manga until chapter 105)
Season 3's second half comes along with the Return to Shinganshina arc. I knew about Erwin dying and Armin getting burnt up. I read the manga that far by the time this came out, so I thought I'd be prepared, but no. The voice acting, the soundtrack, and the animations really added so much more to these scenes.
Last one is in the manga, chapter 105. It's the arc after Return to Shinganshina, where we see what the Marley people are up to. It's a reaaaally slow build-up to what becomes a real explosive battle. These children soldiers get involved as Eren and everyone pulls back after a successful attack. And uh.. Sasha gets shot by a kid and she bleeds out. It didn't feel real to me. I kept reading on afterwards for a few chapters.. but I gave it up eventually. But season 4 is coming in a year or so, and I'll be more than willing to see the last chapters adapted~
Demon Slayer (anime)
It's not a huge main character, matter of fact, I don't think he has an actual name.. I looked up and they refer to him as the Hand Demon. Tanjiro faces him during the Final Selection arc. Really early on in the anime, episode 4.. maybe 5. Tanjiro kills this demon and I expected him to just kill this demon. But he showed compassion and like he held his hand before actually killing him! It triggers a flashback for this Hand Demon and he remembers his brother holding his hand out and it was just so weirdly emotional for me to watch lol but I love it!
Naruto Shippuden (anime)
Episodes 82 and 152. Not so much about the deaths, but the aftermath of their deaths hit me hard. Losing both Asuma and Jiraiya definitely hit hard to some extent, but seeing Naruto and Shikamaru learning to deal with losing their teachers and in Naruto's case, his father figure, that was.. that was something else lol I get chills watching those scenes
Fullmetal Alchemist: Brotherhood (anime)
Strangely enough Nina's death.. didn't hit that hard for me. I mean yeah, it's sad, but I got nothing. I get why other people have a hard time watching it, but yeah, I didn't feel too connected to her to feel it as much.
Envy's death, however. is so damn sad to watch. This cocky arrogant character I came to hate has one of the most heart-wrenching deaths for me in anything. This guy gets reduced to such a small vulnerable creature and he tries his hardest to get everyone to turn on each other, but nothing happens. Ed figures out exactly what all his flaws are. Everything Envy wants is what he can't have, so he lashes out on everyone. And Envy refuses to face those facts, and he cries and feels so ashamed for being jealous of humans, so he decides to kill himself. What hits the hardest for me of this scene is his pitch-shifted voice (it's rather high, since he's a tiny creature) and the music. He nearly sounds like a little child and the emotions are almost accentuated by the altered voice, so him screaming and crying just embodies misery and pain in the scene for me and makes it hit like 10 times harder.