Most Effective Method? Exclude Category and Number of Posts Per Page

Just use a custom query like this:

$exclude_cats="2,52,3";
$posts_per_page="4";
$loop = new WP_Query("category__not_in=$exclude_cats&posts_per_page=$posts_per_page");
if($loop->have_posts()):
    while($loop->have_posts()): $loop->the_post();
        //Do stuff here the_content(), the_title() etc...
    endwhile;
else:
    //Do something here
endif;