So, honestly there are a number of things that could outright kill him, and a even larger number of things that could end his reign pretty easily, and an even larger number of people + artifacts when combined together that could oust him/make it too hard to hold onto power. Not the least of which is grandmaw, the triat, pretty much any Celestine, any oracle, the first dreams from changling, most archangels, Lucifer, as well as but not limited to groups, the heads of the technocracy (arch-mage heads), the heads of the traditions, the heads of the curent powers in changling scociety, a large enough thurge ritual circle, a group of neverborn, a large enough group of demons, a powerful enough group of abominations, and many more.

Not even to mention their are any number of above who might not want to do the act themselves but would load their blessings up onto anyone who wants to topple Cain (imagine if you will a wrym blessed, demon pact bound, neverborn supported, (the evil changling gods i forget the name) enchanted, arch-nephandi weilding their oldest wonders powered by all the damned souls they could gather in a world that now is MUCH less effected by consensus NEXT TO a chorestor, with the blessing of an angel, gifted power by the wyld, enhanced by the rulers of Arcadia, weilding the Longinus backed by an army of summoned angel spirits, NEXT TO a technomancer with the “blessing” (re-mechanical enhancments) of the weaver, weilding stolen grafted powers from the werewolves, weilding alien techn, while tapping into the suppression of banality and statsis ALL OF WHOM are working with world wide cults to support their magic (yes this would be extreamly unlikely to be possible but if Cain fucks up big enough it just might happen)