I would suggest this. You can simplify the hash if you are happy to use the substitution pattern as the top level key. The guts of the approach is to build an alternation RE dynamically and use the match value to lookup the replacement value in a hash. This is typically the fastest approach as you leverage the C code in the regex and hashing engines effectively. Note the sort by longest first so we match on the full 'foobar' not 'foo' or 'bar'.

my $res = {
    re1 => { foo => 'foo_new' },
    re2 => { bar => 'bar_new' },
    re3 => { qux => 'bar_new' },
    re4 => { foobar => 'foobar_new' }
};

my @required = qw ( re1 re2 re4 );
my %active_re = map{ each %{$res->{$_}} } @required;
my $match = join '|', sort{ length $b <=> length $a } keys %active_re;
$match = qr/($match)/;


$str = 'foo bar baz foobar';
$str =~ s/$match/$active_re{$1}/g;
print $str;
[download]