At the 1980 Conference on Lisp and Functional Programming, Kent Pitman presented a paper "Special Forms in Lisp" in which he discussed the advantages and disadvantages of macros and fexprs, and ultimately condemned fexprs. His central objection was that, in a Lisp dialect that allows fexprs, static analysis cannot determine generally whether an operator represents an ordinary function or a fexpr — therefore, static analysis cannot determine whether or not the operands will be evaluated. In particular, the compiler cannot tell whether a subexpression can be safely optimized, since the subexpression might be treated as unevaluated data at run-time.
tl;dr version:
Le jew PITMAN condemns fexprs because he cannot his way into static analysis. But being Lisp is all about direct manipulation of the AST, who the fuck cares about Le static analysis.