So for the sake of completeness, and posterity... and not because anyone cares, here's the final version that I decided fixed things up the way I wanted. Turns out by reordering the substr I was able to remove the space ambiguity I was seeing in one of my example data failures where I was getting nested span tags.

sub spandiffstr {
    my ( $old, $new ) = @_;
    my $span = '<span>';
    my $espan = '</span>';
    ( $old ^ $new ) =~ /^\0*/ and my $subscr = $+[0];
    substr $old, $subscr, 0, $span;
    substr $new, $subscr, 0, $span;
    my ( $rold, $rnew ) = map scalar reverse, $old, $new;
    ( $rold ^ $rnew ) =~ /^\0*/ and my $lsubscr = -$+[0];
    my $losubscr = $lsubscr;
    unless ($lsubscr) {
      $losubscr = length $old;
      $lsubscr = length $new;
    }
    substr $old, $losubscr, 0, $espan;
    substr $new, $lsubscr, 0, $espan;
    return $old, $new;
}
[download]

Thanks for all the fish!