I ended up going with this, because, well, clarity of code won over speed?

sub tweak_links($)
{
    my $text_ref = shift;
    my $modified = 0;

    while (my($key,$value) = each(%main::fixers)) {
        if($$text_ref =~ s|"(http://)$key(["/])|"$1$value$2|g) {  #"
            $modified = 1;
            }
        }
    return($modified);
}
[download]

I'd prefer a pre-compiled regex, if the resulting code was not obtuse.