Your code is invoking O(n squared) behavior. You should use a hash as a set type, instead of linearly comparing each line to the entire other file contents.

As a brief example, the core of your program can be:

my %compare;
my %files = ( a => 'oldfile', b => 'newfile' ); # compare oldfile to n
+ewfile
for my $filekey (keys %files) {
  open F, $files{$filekey} or next;
  while (<F>) {
    next if /^(#.*)\s*$/; # ignore blanks and comments
    $compare{lc $_} .= $filekey;
  }
}
print "Lines in newfile but not oldfile:\n",
  sort grep $compare{$_} !~ /a/, keys %compare;
print "Lines in oldfile but not newfile:\n",
  sort grep $compare{$_} !~ /b/, keys %compare;
[download]

I used this technique in a recent post as well, and you might see it clearer there.

-- Randal L. Schwartz, Perl hacker