My hardest/most time consuming achievements (in no particular order):
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Key To The City
You completed GTA IV to 100%.
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War Hardened (Call of Duty 2)
Finished the Single Player Campaign on Hardened or Veteran difficulty setting
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Deep and Hard (Call of Duty 4)
Complete the game on Hardened or Veteran difficulty
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Medal of Valor (Mass Effect)
Complete 1 Mass Effect playthrough on the Insanity difficulty setting.