<?php $loop = new WP_Query( array( 'post_type' => 'portfolio' ) ); ?>
    <?php while ( $loop->have_posts() ) : $loop->the_post(); ?>
    <div class="four columns">
        <?php the_content(); //along with other stuff in looped div ?>
    </div>
<?php endwhile ?>

<?php $counter = 1 ?>
<?php $loop = new WP_Query( array( 'post_type' => 'portfolio' ) ); ?>
    <?php while ( $loop->have_posts() ) : $loop->the_post(); ?>
    <div class="four columns <?php if ($counter % 4 == 1){echo 'alpha'}else if ($counter % 4 == 0){echo 'omega'} ?>">
        <?php the_content(); //along with other stuff in looped div ?>
    </div>
<?php $counter++ ;
endwhile ?>

<?php $loop = new WP_Query( array( 'post_type' => 'portfolio' ) ); ?>
    <?php
        $i = 0;
        while ( $loop->have_posts() ) : $loop->the_post();
           if( $i % 4 == 0 )
             $class = 'omega';
           else
             $class = '';
        ?>
    <div class="four columns <?php echo $class ?>">
        <?php the_content(); //along with other stuff in looped div ?
           $i++;
         >
    </div>
<?php endwhile ?>

div#test > *:nth-child(4n+4) {
    color: red;
}