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Super Metroid. It's music makes you feel so isolated when playing. Sometimes I have to abruptly quit the game because I start getting antsy after a while. (same goes for Metroid Prime)

If there's one thing Nintendo promised with the metroid games is that the music really does make you feel like you're all alone in a deserted planet. The music makes you feel anxious as hell, and for me with anxiety problems, it's not pretty.