Arithmetic isn't more difficult with S-expressions, and in fact complicated arithmetic expressions are easier to format across multiple lines to make their organizations recognizeable. It also naturally supports N-ary operations. For instance (* a b c d) could be a matrix multiplication which chooses the optimal order for the decimation, taking into account all arguments simultaneously.
I like lisp and prefix notation in general, but I definitely still prefer reading large mathematical expressions in infix. Its really just a matter of preference.
Most maths applications written in Lisp use infix/mixfix syntax for the languages they implement, too: Macsyma, Derive, Reduce, Axiom, ...
Implementation of those slightly diverges. Macsyma internally is largely written in Lisp syntax, where for example Reduce is written in RLisp (which is a Lisp written on top of Portable Standard Lisp), which does not use s-expression syntax.
