What is the simplest way to typeset an entire document in sans-serif?

\renewcommand{\familydefault}{\sfdefault} will switch to using sans-serif for everything except mathematics. The sans-serif will be computer modern sans unless you also put \usepackage{helvet} in the preamble in order to make the default sans be Helvetica (or \usepackage{avant} for Avant-Garde, etc.

In ConTeXt you obviously use \setupbodyfont. This will not affect math mode.

\setupbodyfont[ss]

\starttext

Sans-Serif

\stoptext