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Infamous 2 opens in Empire City as a massive explosion rips through the town signaling the birth of a new evil. Nearly escaping death by the dark entity known as The Beast, Cole flees the city. Upon leaving, Cole discovers that The Beast has destroyed Empire City and is heading down the coast annihilating everything in its path.

In an effort to stop The Beast from destroying mankind, Cole heads to New Marais in search of a scientist who is believed to hold the key to defeating this dark entity. As the mystery of The Beast unfolds, Cole must learn to harness his powers for the sake of mankind.