There can only be one.
The plot twist that made System Shock 2 get on most "best horror games of all time" lists. A total mindfuck that still hasn't been matched by most games made today - learning that not only was your Mission Control operator dead, but that she had killed herself before the main plot started, and the antagonist of the original game was back, coupled with quite possibly the best physical reveal ever in the gaming medium (the walls fall away around you, replaced by computer screens and SHODAN's face).
"THE POLITO FORM IS DEAD, INSECT."