Yeah, personally I'll probably make another playthrough, if only to see how they turn out in the sequels.
I also did two main playthroughs with different classes and different genders; it's fascinating to see what the differences can be between, say, a female Infiltrator and a male Vanguard.
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I think even if the game doesn't have much replayability, I'll probably go back to it once or twice if simply to relive the memory of playing it - if the story/gameplay is actually enjoyable/memorable enough. I'll probably play through Human Revolution again, maybe another time just to see how going rambo will be different.
Perhaps one of the reasons I might not play the game again is if it's emotionally draining, or simply takes up so much time. As much as I love, say, Fallout New Vegas, it took me in excess of 150 hours just to go through every nook and cranny and explore the DLC.
Another game that sticks out in my mind is Lost Odyssey. That game is simply just a whirlwind of depressing emotions surrounding the characters. Even though that game is such a triumph of the old turn-based JRPG, I just can't bring myself to play the game a second time.