The biggest unsolved geographical mystery is a question that can be answered differently by different people. This depends on each person's perception and interests. These are the keys to determine what is the biggest. One of the unsolved geological mysteries for me is the core of the earth.
For time eternal, people have guessed and have tried to understand what is far beneath the earth. For scientists that have interest in studying the earth's core, it is a never ending feat as that is a place where they cannot travel to. There are numerous other mysteries of science and geography that people have wondered about for ages, but we just don't have a definitive answer for these matters.