Improving on this "catch all"?

The rule you have is actually pretty clean, if a bit hard to follow. You could use a switch statement with indentation and spacing instead. It might be a little easier to follow and slightly faster than multiple if/elseif/else's.

when HTTP_REQUEST {
    Parse the HTTP host header value
   switch [string tolower [HTTP::host]] {
       Host was site1
      site1.domain.com {
          Set the pool to site1 pool
         pool pool_site1.domain.com
      }
       Host was site2
      site2.domain.com {
         if {[HTTP::path] eq "/"}{
            HTTP::uri "/pathtosite/site2"
         }
         if { [matchclass [IP::client_addr]/16 equals $::mySubnets] }{
            pool pool_site2.domain.com_internal
         } else {
            pool pool_site2.domain.com
         }
      }
       Host was site3
      site3.domain.com {
         pool pool_site1.domain.com
      }
       Unknown host, reset the connection
      default {
         reject
      }
   }
}

Aaron