Dante didn't take well to finding out that Trish was working for Mundus. Even though he saves her because she looks like his dead mother, he doesn't want to see her ever again, going so far as to put her at gunpoint, shouting that even if she looks like his mother, Trish is just a soulless demon, then drops his gun, and walks away in anger and sadness.
Trish even gets thatlook on her face after that last statement.
And then she takes an attack from Mundus that was aimed at Dante, and apparently dies because of it. His tears after the first two battles with Mundus can make anyone weep.
Followed by Dante mourning over Trish, leaving the Perfect Amulet and the Sword of Sparda (both mementos of his family) with her.
Dante: (places the Amulet over Trish's heart) This was my mother's...now I'm giving it to you. (plants the Sparda into the floor next to Trish's body) My father's also here now. Rest...in peace.
When Trish tries to apologize to Dante for selling him out to Mundus, she cries Tears of Remorse.
Dante realizing who Nelo Angelo really was... his brother, Vergil... after he's destroyed him. Making things worse is Dante briefly recalling one of the few good memories he had left of Vergil, before their falling out; the birthday in which he and Vergil received the halves of the Perfect Amulet, a gift from their mother, Eva. Though the brothers also briefly talk about wanting chocolate for their birthday, this dialogue comes off more as a tear-jerking moment than a heartwarming or funny one given the context.
From the bits of Dante's backstory, he was a happy and carefree child. Then he loses his family during a demon attack and the rest of his life became a lot worse. In the non-canon novel, Dante watched his mother be torn apart by demons right before his eyes. He's only eight-years old at the time.
It seems to be the same for Vergil, which makes it even worse. Depending on whether you consider the manga canon, it gets very, very worse... and never really gets better.
While the last boss fight against Griffon is a pain in the ass, and even if Griffon himself is a demon, there is just something tragic about his death. After being gravely wounded by Dante, he begs Mundus to help him, to give him just one last chance to prove his worth and destroy Dante. Mundus cruelly denies him this, shortly before zapping him to cinders while Griffon is begging Mundus not to. If you did not think Mundus was an utter bastard before, you will now. Dante certainly did. Mundus also has the audacity to laugh evilly after coldly killing Griffon.
