I recently started using ExtJS, with CGI::Application and JSON. It works nicely, and abstracts away a lot of the pain of cross-browser compatibility, though the large file size can be a problem (there are other, lighter toolkits that may better serve your purpose). Here's a 30 second example that gets you AJAX style updates:

callbackFunction = function(options, success, response) {
  if (success === true) {
    var data = Ext.decode(response.responseText);
    doSomething(data);
    // or
    Ext.get('contents-div').dom.innerHTML = response.responseText;
  }
  else {
    Ext.MessageBox.alert('Error', 'Something blew up.');
  }
}

Ext.Ajax.request({
  url: '/path/to/cgi',
  callback: callbackFunction,
  params: { rm: 'ajax_function' }
});
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The Perl part, assuming you've tagged this sub as a runmode:

sub ajax_function {
  my ($self) = @_;
  my $data = doStuff();

  # or you could return HTML
  return $self->{json}->objToJson($data);
}
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It has other cool stuff built in, like the ability to automatically generate fields and labels for a form, and bind the validation and submission to callback functions, visual effects, data stores and interfaces for all different kinds of sources... it actually got me interested in learning JS. Pretty cool stuff.