What is your religion's most significant work of art and why?
I am afraid that I am unable to provide you with the specific answer you hope for.
Art promotes seeing beyond the obvious to what lurks in the crevices of the human-divine experience. Art offers an unmatched source of history and experience as well as a resource for transformation. To reap its benefits requires risk, imagination and courage, qualities felt in art, known through the activity of God with our human qualities as well that which sustains the ongoing development of ones spirituality.
Throughout history, art has been used to express the making of something, usually with materials, words, sounds or movements. So, how do we arrive at identifying one piece of art in our faith which is its "most significant"? To identify it, for any one individual, I suspect it would be, in the context of our faith, the one piece which helps us most connect with God. But, that changes for each individual. For some, it could be the architecture itself (such as Michaelangelos St. Peters Basilica or the Sistine Chapel Ceiling in Rome), for others it could be a painting (like Leonardos The Last Supper) or a sculpture (such as Michelangelos Pieta). Others might point to certain musical compositions, others to works of poetry or prose. Then, some experts could attempt to identify the highest monetary value; does that equal "most significant"?
Therein lies my own answer. Most of us are simply unqualified to pinpoint "one" work of art, either in Rome, in the Holy Land or any other country for that matter. I prefer to think that we have been blessed with many, many gifts and all of them help us to discover their authors understanding of an aspect of the mystery of God. In the measure that they draw us into it, they are most significant!