Episode 8 in general is this. You have Mamoru desperately trying to get Maria's attention only to find his efforts in vain, Shun and Satoru breaking off their perfectly healthy relationship because of Shun's Sanity Slippage, and the above example which definitely foreshadows that something horrible is going to happen to Shun.
Episode 9. Saki's mother. "I don't want to lose any more kids... no, I just don't want to lose you!"
Episode 10. Oh God, Episode 10.
Even before that climatic moment, there's Saki calling herself out on her inability to save Shun. To see a 14 year old girl walk so close to the Despair Event Horizon is hard to watch.
Subaru's death to a Fujoneko was pretty saddening to watch as well, especially when Shun takes a moment to reflect on his pet dog's Heroic Sacrifice.
On top of all that, one would never expect Shun, of all people, to resign himself to his fate and feel so broken because of it. Seeing him do just that is heartbreaking.
Of course, all of these moments lead to the biggest Tear Jerker thus far in the series: Shun's death. Seeing Shun tear up before dying as Saki screams his name in horror is going to cause one to shed tears for a very long time.
Episode 11 doesn't have quite so much to sob at, but there's still something harsh about the fact that Shun is only refered to as "X" even in the end credits.
Episode 12 follows suit with Kutegawa Izumi, the first Gouma (Karma Demon) recorded in the village. An otherwise sweet, perfectly normal girl, her PK powers warp everything around her. Watching her resort to suicideto save the village is... depressing to say the least. Not to mention Saki's tears after Tomiko finishes the story.
Oh, and Izumi's family? All mutated and killed by her unknowingly. You know it's incredibly sad when the Ethics Committee can't bring themselves to deliver the news of the death of Izumi's family to her.
While memories of Shun were erased from everyone after his death, it's clear that Saki still his presence in the group. As she hears about Izumi, she breaks down because she's unable to fully remember Shun.
Episode 16: Maria's final letter to Saki. All of it. From Kana Hanazawa's superlative and emotional voice-acting to Maria's reasons for leaving Kamisu 66, it's brutally difficult not to cry.
Also, the insert song (later revealed to be the series' second ED). Take a look at those lyrics and the images of Maria and Saki playing as children. You won't last a few seconds before tearing up.
"When I noticed that the two of us were skiing side-by-side, I realized what I had truly been afraid of. My world consisted only of Sage Academy, if one excludes my parents. And within that world, I could only call those of Group One my friends. One by one those friends disappeared, until only Satoru and I were left. I hated it I didn't want to lose any more friends and loved ones... The two of us were alone in this world."
As if that wasn't painful enough already, at one point Saki starts to see Shun in Satoru's place as she follows him, and tries to reach out to him. In other words, this episode likes to remind us of the other major Tear Jerker ep on top of being very sobworthy in its own right.
Dvorak's ''From the New World'' theme returns, only this time to signal the end of another fruitless day of the two trying to find Maria and Mamoru. And, given Tomiko's deadlines, Satoru and Saki are out of time: Mamoru and Maria are gone for good.
As they rest in the makeshift igloo, Saki asks Satoru if the two will forget Mamoru and Maria just like they did with Shun. Let the floodgates be opened.
Basically the entirety of episode 16, from the note to the memories to the helplessness and lonesomeness that Saki and Satoru feel.
Episode 18: Through DNA testing, Tomiko concludes that the bones given to them by Yakomaru in fact belonged to Maria and Mamoru. In other words, two more of Saki's friends are dead. It's not hard to see why Saki was so shocked after hearing the news.
Episode 20: Upon being critically injured, Tomiko knows she has very little time left before Yakomaru's army and his Akki come to finish Kamisu 66 off. Seeing Tomiko give her position to Saki before sending her and Niimi (Tomiko's assistant) off in spite of their protests is heartbreaking.
The Reveal in Episode 21. That Akki? That bloodthirsty, nightmare-inducing Akki? SHE'S MARIA'S AND MAMORU'S DAUGHTER.
In episode 23, Saki finally remembers Shun in the backdrop of Tokyo's ruins and this awesome piece of BGM. The entire sequence is definitely one of the most powerful moments of this series.
To say nothing of the death of Mamoru's and Maria's daughter. Groomed to be Yakomaru's secret weapon, this girl will never have an opportunity to live a normal life, go to school, or even knew who she was in the first place. The fact that she greatly resembles her mother doesn't help at all.
Yakomaru: "We are not beasts nor slaves. ...WE ARE HUMANS!!!"
Made incredibly worse when you realize the truth about the Bakenezumis' origins.
A fan-art example: One fan-made wallpaper◊ depicts Mamoru and Maria playing with their kid. Tears will be shed, especially if you know that Mamoru and Maria were murdered not long after their child's birth and thus would never have the chance to do just that. Knowing what Yakomaru did to their daughter only worsens the tears.