It's almost a colloquialism that there are four holy cities in Israel.
If, indeed, there is some significant message derived from the historical importance of these cities that imparts in them some holiness, why aren't there more? For instance, given the fact that it was home to the Mishkan for such a long time, I'd expect Shiloh to be on the list. In addition, given the fact that the Sanhedrin convened there after the destruction of Yerushalayim, I might also expect Yavneh to be on the list.*
