This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Resident Evil: The Darkside Chronicles
Annette Birkin guiltily and weakly begging Leon and Claire to tell her daughter how she was sorry she was a failure as a mother and that she always loved her, all while bleeding out after her husband turned G monster mortally wounds her.
Worse is when Sherry is told about her death by Leon. The news is difficult for the poor little girl to take as she looks for comfort in Claire whom she after the events of the game sees as the only thing close to a mother figure.
Alfred Ashford realization that Alexia never truly returned to him and that he was masquerading as her the entire time once he looks into the mirror. Unlike Code Veronica where the scene came across as silly due to poor voice acting here he simply screams in horror and runs away.
What truly hammers in the sadness of this scene is Claire herself sounds rather sympathetic to the the poor psychotic bastard as she states "he couldn't bare the fact his sister was dead". Even Steve nods his head in agreement. Makes sense when you understand Claire's own relationship with her brother and how she must have felt not knowing if Chris was alive or not.
After everything he went through to see the plan through and despite his absolute loyalty and love for her Alfred Ashford is strangled by his own sister's T-Veronica tentacles after he awakens her. What makes this worse is that Alexia's reasoning for her action was "he really wasn't much fun" and that he didn't wake her up on time. Even Claire sounds disgusted when she hears all this.
By means of a video recording which plays during the boss battle against Alexia, Alexander Ashford (her father) confesses that he realized what the person his own daughter had become and regrettably took steps to insure that her mad dreams never reached fruition by means of the Linear Launcher which he urges whomever is watching "whether you are on Umbrella's side or not, please help her". Worse is you already know what became of Alexander.
What happens to Manuela in Darkside Chronicles if you get the bad ending. Make sure you take less than ten minutes to avoid it, please.
Even Krauser himself looks greatly saddened by Manuela's death on board the helicopter should you get the bad ending.
The huge blob of a monster you fight during Operation Havier? it's Hilda, Manuela's mother, and she sheds a tear after Leon and Krauser are forced to kill her and she has a brief moment with her daughter.