First, is that it's too "meta" in that one can shape it to be just about anything they want. This can make it difficult for others to read your code, for they have to know your mind's style. Our typical "office" languages tend to hard-wire idioms, such as control structures (if, while, case, try, etc.) which make it easier for other readers to digest. It may be less parsimonious (more code), but it's overall easier for an outsider to come in and read it.
Second is that nested lists are the wrong base structure for humans. Our natural languages are closer to maps or ordered maps (AKA "associative arrays"), not nested lists. I was working with others at the C2.com wiki to form something similar for maps: a meta-heavy map-oriented language. We nicknamed the project "MASP". C2 fell apart, but I have some new ideas for MASP that I may write up one of these days.
MASP may never go mainstream because of its heavy meta-ing, but could be great for experimental, hobby, and rush-to-market startup projects. Paul Graham has said Lisp's meta ability gave him an edge in the "stores race". Being first-to-market matters in dot-com-ville more than team-friendly code.