1. Was any crusade at any point close to threatening the Hedjaz, Medina, and Mecca?
In 1182 (IIRC), Raynald de Chatillon led an expedition into the red sea, with the intention of disrupting mislim trade, siezing the holy cities, and taking the body of the prophet back to Kerak. Though initially successful, the raid was eventually defeated after a coherent response was gathered (Raynald having already made good his escape).
2. Suppose they somehow took the cities. A more pragmatic leader is in charge of it, and while they keep the cities, they allow Muslim pilgrims to continue their hajj, with the exception that Christians are now allowed to enter and live in Medina and Mecca. How will the Islamic world respond?
The mother of all jihads is called to reclaim them. Though this may not amount to anything, Mecca and Medina have now become prime targets for any islamic ruler. The cities are probably too far away from the levant for the christians to keep the area supplied and in communication, so sooner or later they will fall. Bad things are going to happen to the crusader states as well.
Now, raynald's raid was not about conquest, for the very good reason that he was lacking in numbers and the targets would be impossible to defend. His goal was more to take the cities, loot as he pleased, and then retire to his own lands with certain relics. IIRC he was even planning to hold the body of the prophet hostage and charge muslim pilgrims to see it. This will provoke a similar response from the islamic world, but results in a different scenario. kerak is a rather difficult nut to crack, and the christians may somehow hold out. The medium and long-term effects of this on the middle east will be interesting.