Split wordpress loop to multiple layouts

Just create 2 queries using the “offset” parameter and separate them by:

<?php wp_reset_query(); ?>

Display posts from the 4th one (offset is starting from 0):

<?php $query = new WP_Query( 'offset=3' ) ); ?>

EDIT: Here’s some sample code:

<?php query_posts('offset=0&showposts=2&order=ASC'); ?>
<?php if(have_posts()) : while(have_posts()) : the_post(); ?>
    <p><a href="https://wordpress.stackexchange.com/questions/61605/<?php the_permalink(); ?>"><?php the_title(); ?></a></p>
<?php endwhile; endif; ?>

<?php wp_reset_query(); ?>

<?php query_posts('offset=2&showposts=4&order=ASC'); ?>
<?php if(have_posts()) : while(have_posts()) : the_post(); ?>
    <p><a href="https://wordpress.stackexchange.com/questions/61605/<?php the_permalink(); ?>"><?php the_title(); ?></a></p>
<?php endwhile; endif; ?>

That’s it. You’ll have 2 posts which you can style any way you want, and the next four, which, again, you can style differently.