open IN, $infile or die "Can't open input file: $!";

##</code><code>##

my %set;
my $substit = "";
for (1..26) {
    my $randchar;
    do { $randchar = chr((int rand 26) + 65) }
        while $set{$randchar}++;
    $substit .= $randchar;
}

##</code><code>##

my @alpha = split //, "ABCDEFGHIJKLMNOPQRSTUVWXYZ";

##</code><code>##

my @crypt = @alpha;
fisher_yates_shuffle(\@crypt);

##</code><code>##

my $substit = join '', @crypt;

##</code><code>##

sub fisher_yates_shuffle {
    my $array = shift;
    for (my $i = @$array; --$i; ) {
        my $j = int rand ($i+1);
        next if $i == $j;
        @$array[$i, $j] = @$array[$j, $i];
    }
    return join '', @$array;
}

##</code><code>##

Benchmark: timing 5000 iterations of orig, f_yates, hash...
      orig: 33 secs (23.60 usr  0.00 sys = 23.60 cpu)
   f_yates:  5 secs ( 2.88 usr  0.00 sys =  2.88 cpu)
      hash: 13 secs ( 5.68 usr  0.00 sys =  5.68 cpu)