So here's a bit of an out there, not really flushed out theory on the skulls, that also involves some assumptions on other things.
First, for the sake of this argument, let's assume that Isis and Osiris are in fact Dee's Elders, i.e. Dark Elders, and that the Witch is in league with them.
The Witch "spent fortunes" trying to destroy the skulls (and other archon tech), and that happened after the fall. So let's also assume that it happened after Chronos gave her the gift of seeing the timelines.
The Witch has a vision of Sophie and company using the skull to track Josh to Enoch Enterprises, who then get there just in time to prevent Coatlicue from being summoned, thus thwarting Dee's plans. In other visions she may have seen Dee as being an aide to the Dark Elder's, so in her mind they were also thwarting the Dark Elder's plans.
So she goes on a mission to destroy all the skulls, not because they are "dangerous" to the world, but because without the skull, the Flamel's and Sophie would not be able to track Josh, thus allowing Dee's plan to succeed.