At one time, Malthael, archangel of wisdom, was the leader of the Angiris council and the most respected angel in all of the High Heavens. However, when the worldstone was destroyed (at the end of Diablo 2), he vanished from heaven, and his fellow angels could only speculate as to where he had gone.
As of now, it's uncertain what exactly Malthael did or saw during his absence, but it couldn't have been anything good since, when he finally reappeared, he called himself the archangel of DEATH.
Since Diablo was defeated and the seven evils of hell were imprisoned in the black soulstone, Malthael reasons that humanity (who, may I remind you, carries both angel and demon blood in their veins) is the strongest "demonic" force left in all of creation. Therefore, if humanity is eradicated, the angels will claim final victory in the eternal conflict between heaven and hell.
Naturally this is pretty bad for us humans, so we've gotta take him down.