I think I figured it out. Thanks to Yanick and to the link referenced in my other answer (Kludgy Workaround #2) for the inspiration. Here's the recipe:
Create a single wrapper file for use in your entire project, and make it:
<% IF layout %> <% INCLUDE "$layout" %> <% ELSE %> <% content %> <% END %>
Within your route:
return template('mytemplate', { layout => 'layouts/some_layout.tt', param1 => data1, param2 => data2, ... });
And bingo, you're done. Leave out the layout parameter, and will get no layout at all.