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"YOU PICKED THE WRONG HOUSE, FOOL!" is a line from Grand Theft Auto: San Andreas that became quite popular and has been rarely seen around the internet these days. Unless the slight occasion in Pyrocynical Videos.
The Meme itself is when you enter the protagonist (CJ)'s house, Big Smoke carries a baseball bat and comes towards you and shouts "YOU PICKED THE WRONG HOUSE, FOOL!" .