Unsurprisingly given my avatar mine would probably be System Shock 2, I've lost count of the number of playthroughs. Fantastic. Another contender is bizarrely probably UFO: Afterlight, played it through 5 times. There's just something about terraforming Mars that plugs into my geek brain and fills me with joy watching the Noctis Labrynthus slowly filling with water. Sad. I know.