Is this like a Christian trying to blow up the Vatican?, Why are they doing this is, it that segregated or sectarian?.
ISIS has it out for Saudi Arabia most of all (it's not the Saudi state that sponsors them directly, it's Saudi billionaires who do so privately while the Kingdom turns the other way, while the Kingdom also promotes the clerics that teach the extreme version of Islam that leads to groups like ISIS).
Also because they're extreme enough to see the holy sites as potentially idolatrous, the idea that people are putting these sites before Allah. Anything that has power as a religious symbol is anathema to them because it flouts the prohibition on idolatry, and that is the Grand Mosque and the Dome of the Rock and other such places.
I'm sure there are Christians out there who'd love to blow up the Vatican for similar reasons, a belief that the Catholic Church is injecting itself between people and God. At the extreme end of Judeo-Christian family tree, anything of worldly importance is potentially corrupting and evil.