The admin-ajax.php handler is a bit heavy, especially if you’re using AJAX on every page load. I am working on a project now that has multiple caching mechanisms and the only way to update the original server is to POST to the server. Since admin-ajax.php invokes the admin_init hook, it loads a lot of unnecessary items for AJAX call. Here’s the light-weight version of admin-ajax that I created to handle my plugin’s AJAX calls. Save this as request.php in your plugin folder.

define('DOING_AJAX', true);

if (!isset( $_POST['action']))
    die('-1');

//relative to where your plugin is located
require_once('../../../../../wp-load.php'); 

//Typical headers
header('Content-Type: text/html');
send_nosniff_header();

//Disable caching
header('Cache-Control: no-cache');
header('Pragma: no-cache');

$action = esc_attr($_POST['action']);

//A bit of security
$allowed_actions = array(
    'action_1',
    'action_2',
    'action_3'
);

if(in_array($action, $allowed_actions)){
    if(is_user_logged_in())
        do_action('plugin_name_ajax_'.$action);
    else    
        do_action('plugin_name_ajax_nopriv_'.$action);
}
else{
    die('-1');
}

To use this you obviously would hook into these actions doing the following:

//For logged in users
add_action('plugin_name_ajax_action_name', 'function_callback_name');

//For logged out users
add_action('plugin_name_ajax_nopriv_action_name', 'function_callback_name');

You will need to craft your AJAX request as follows:

jQuery(document).ready(function($){
    var data={
         action:'action_name',
         otherVar: varValue
    };
    $.post('http://url/to/your/plugin/request.php', data, function(response){
         alert(response);    
    });
});