In terms of the Imperial Hierarchy and the Inquisition then Chaos is probably perceived as the greatest threat. It's the enemy within as well as without.
It was Chaos which turned Horus, who turns Astartes, that causes secret cults to ferment and planets to rebel, Chaos which posses psykers and corrupts the mind and soul. Chaos is the cancerous underbelly gnawing at the Imperium. The High Lords of Terra live in fear of Abaddon finally reuniting all the Legions and renegades and overwhelming Cadia.
In local areas there may be greater, or more pressing threats but for the leaders of the Imperium and the empire in general it's Chaos.
@Vaz, why would Maccrage hold the Dark Eldar to be a sever threat?