#!/usr/bin/perl
use warnings;
use strict;

my $file = 'datei';
my $tmpfile = "$file.tmp";

my %changes = (
    'eintrag1' => 'XXXX',
    'eintrag2' => 'foo',
    # etc.
);

open(my $fh, '<', $file) or die $!;
open(my $th, '>', $tmpfile) or die $!;

LINE:
while (my $line = <$fh>) {
    KEY:
    for my $key (keys %changes) {
        if ($line =~ s/($key\s*=\s*)[^#\s]+/$1$changes{$key}/) {
            print $th $line;
            next LINE;
        }
    }
    print $th $line;  # kein Match
}

close($fh) or die $!;
close($th) or die $!;
unlink $file;          # oder als Backup speichern
rename $tmpfile, $file;