Playing GTA IV,not counting the countless and inevitable killing sprees and massacres, I'd pick some random person off the street, shoot them in he gut or knee cap then follow them as they slowly crawled away before emptying whatever gun I was using into their face.
From Saint's Row 2 (again discounting the senseless killing sprees) I liked planting a satchel charges on bystanders, laugh as they ran around in a panic then detonate the charge when they were near a crowd. I also liked taking the armored car with the turret (can't remember the name) and go on an extended drive by.
From Prototype I enjoyed picking up people (or cars) off the street, climb the closest and tallest building then throw them off (while using the increased strength power)
From Fallout 3 I enjoyed wiping out every major civilization I could. During one play through Megaton( except for the kids), Rivet City, Republic of Dave, Canterbury Commons, Andale (they had it coming) Tenpenny Towers, Oasis, Paradise Falls, Ghoul city and the ex-slaves community (blanking on their name) were completely devoid of life.
Finally, in both BioShock games I harvested every little sister and killed everyone I met.
Almost forgot, several times in Assassin's Creed 2 I enjoyed killing those damn bards, I particularly enjoyed poisoning them and watching as the jerked and flailed around before dying.