If it starts with #!, leave it alone. If the line starts with a #, its a comment so delete it. If you find a # elsewhere, and is preceded by a ; (possibly with whitespace in between), hack off the end of the line. That should take care of 99% of your problems.

This doesn't even begin to solve the problem. That won't handle this very legal example:

#!perl -w
use strict; # Always!

# Call method foo like this:
# my @results = foo( $arg1, \%hash ); # foo in array context
sub foo
{
    my ( $arg, $hashref ) @_;
    $arg =~ m/some regex   # with true embedded comments
              on multiple lines/x;
    $arg =~ m/some regex with a # sign in it./;
    $arg =~ m/some regex with a ; # combo in it./;
    my $result1 = "a string with; # in it";
    my $result2 = q; # nasty!;;
    # this comment has ' ' as the first char.
    return ( $result1, $result2 ) # no semi-colon!
}
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And it gets worse, much worse. I didn't even mention the backslash escape problems.