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Tear Jerker: Dead Space
Finding out that Nicole was Dead All Along in Dead Space. Despite being a Heroic Mime, You can help but feel sorry for Isaac at the part.
Nicole: I didn't want it to end like this. I really wanted to see you again...just once. I loved you. I've always loved you.
The animation Isaac goes through during the revelation - even though you never see his face, his body language speaks volumes for just how badly it hits him. Even worse if you read his in-game diary: he knew Nicole was dead, but kept himself in denial up until that point. Ouch.
The audio log from the poor bastard who cut all his own limbs off to keep himself from being a danger when he got infected—and only asks that someone tell his wife and kids that he loves them.
What makes it even worse? It didn't work.
Finally finding Acting Chief Engineer Jacob Temple and Dr. Elizabeth Cross, whose audio logs you've been listening to through half the game. After going through hell to find each other again they get captured by Dr Mercer and killed off right in front of you.
In the colony, in the room where you find Neumans emergency broadcast, there is a writing on the wall addressed to someones father, to not leave things unsaid.