If you think that the guy who came back was Asch, then Tear's tears at the end can totally be considered this as she realized that Luke really is dead, and she'll never see him again.
At Luke's lowest point he finds out he's a clone and his childhood that he thought he forgot never happened., the person he respected and admired the most had been lying and deceiving him all along, he killed ten thousand people, everyone hates him, they prefer the original over him and the only person who might care is having her doubts.
Asch's reveal is made even worse in the anime as you watch Luke relive all the hints leading up to his shattered identity as a replica - being unable to regain his memories, Legretta calling him a defective thing - in the middle of a total meltdown.
The worst part is probably playing a second playthrough and knowing what's going to happen but not being able to do anything about it.
If that part of Abyss makes you cry, then...well...here's hoping you didn't get attached to some of the other characters.
Ion's death. If you can believe it, it's even worse in the anime - at least in the game, Mohs is right there for you - and the party - to focus their Unstoppable Rage upon. In the anime, he leaves without taking the chance to gloat, letting the event hit you in the gut with all the force of a sledgehammer.
Ion's Memorial Service. Anise asks Tear to sing her Fonic Hymns, saying that Ion loved them, and the rest of the party convinces her that her songs can be a prayer to the departed. She agrees, even though she doesn't fully understand all of the parts of Yulia's hymn. Leads to a heartwarming moment, as Tear finishes singing, the voice of Ion thanks her and unlocks the Fifth Fonic Hymn: Judgment for Tear.
Florian, another of Ion's replicas, is very heartwarming, specially in his relationship with Anise, but it can be quite the player punch seeing him acting like a child and using Ion's clothes, especially since, unlike Sync, you never forget he is just like Ion, just a lot more na´ve.
The Tower of Rem. This Tower's arguably worse than Symphonia.
Not just the Tower of Rem, but the scenes preceding and following it, as well. Tear is heartbroken knowing that Luke is going to die and then Asch tells Luke to die in his place. After realizing that he wants to live, Luke finds out that he's actually dying; the hyperresonance created such a tremendous strain on his body that his fonons are separating and he will eventually fade out of existence. He doesn't want anyone to know because he's afraid that they'll treat him differently.
Even worse is the timing. Luke finally realizes his own self-worth, and truly wants to live, and keep on living... and learns, right at that moment, that he is going to die. Slowly, but inevitably, and before his time.
The conversation with Jade before the Tower, who has just proposed that Luke commit mass suicide, rather than Asch. Luke asks Jade if that's really what he thinks is best, expecting a 'yes'. Jade does say yes, and then...
Jade: That's what I would say if I was an emperor, with a country and people to look after. As your friend... I feel compelled to stop you.
The ending. First with "You have to come home. You have to! I'll be waiting... always," then "Luke...I love you," and then the happy tears after the credits.
That ending, depending on how you interpret it, it's a big case of Downer Ending or Bittersweet Ending because Luke dies. The contamination sidequest reveals will choke you up when Jade says the only things that will be left of Luke are his memories. It doesn't help that after the credits, everyone's happy (save for Jade, whose really ambigous expression can be interpreted as happy or not so much) and thinks it really IS Luke.
The ending is a different flavor of bittersweet depending on how you interpret the identity of the person- if it's 100% Asch, then Natalia gets her beloved back, but Tear doesn't. If it's 100% Luke or Luke's mind in Asch's body (the most common), Tear gets her beloved back while Natalia doesn't. Either way, his existence will serve as a constant reminder of what might have been to the girl who loses out- especially sad for Natalia if you went with the last one.
Luke's turning point, especially the part where he realizes everyone prefers the original over him. "It's no wonder everyone got sick of me and left me behind." The start of a nasty inferiority complex for Luke...and one that can resonate with some people - and so, Luke's decision and the resulting Important Haircut leads to a very touching moment.
Asch's death. Even after spending the entire game blaming Luke for taking over his life, he STILL ends up sacrificing himself so that his replica can move forward. He finally accepts Luke for who he is, and puts his faith in him as he's dying ("Looks like I had a little trouble... The rest is... up to you.)
The scene when Tear confronts Luke about his condition and the following skit: when Luke is afraid of being treated differently because of he's eventually going to disappear and Tear is angry at herself for being powerless to help Luke.
"Class M and Class I's first and final cooperation together." Made all the worse in the anime.
The death of Arietta. In the anime, it's even more heartbreaking as Arietta hallucinates Ion and her animal family with her, reaching out to them, and then dies at that moment. It's even sadder by the fact she died without ever knowing the Ion she knew and loved was already dead.
"You're the only Ion that matters to me." She's a real asshole to Luke after Akzeriuth, but when the chips are down, Anise is a good person. Guy also deserves a mention for one of his lines during the handful of introspective scenes he has with Luke in Aramis Springs: "Replica or not, you're real to me."
Frings' death. It's bad enough as mandated by the plotline, but you have the option of spending an entire long sidequest chain getting him together with General Cecille. To have done all that work for them, and seen the honest joy as they overcame the obstacle of being in opposite armies, to talk to Cecille who is so happy that she and Frings are going to be able to marry... it makes his death really hit that much harder.
Oh yeah, it's also on Nightmare Fuel page, but the kid in Akzeriuth who dies by sinking into the mud.
Mingled Nightmare Fuel and this, but the fact that there are people who just accept deaths and especially the war because 'the Score said it would happen'.
Luke's journal entry from the night before the final battle. He almost decides to tell Tear that he loves her, but the fact that he doesn't have much time left stops him believing that all he'll do by telling her is break her heart when he does die.
And then she tells him she loves him right before she's forced to leave knowing that it's overwhelmingly likely that he'll die releasing Lorelei and she'll ever see him again.
The journal entries from Luke detailing his dilemma over his impending death.
Luke: Tear told me not to keep anything from her anymore. Yeah, I guess. Now that she's learned my biggest secret, I don't have anything...well, only one thing to hide from her. Thanks, Tear.
There is a flashback in the anime where after being kidnapped to Choral Castle Asch ventures home to his parents, only to be shooed away by the guards. He climbs up a fence wall to discover he was replaced by replica Luke. His heart just breaks.