jQuery is the right direction, but the strength of Drupal is based on doing things "the drupal way", which means, I guess in your case, to use Views as the origin for the thumbnails using imagecache + lightbox, and somehow change the main "frame".
I used jcarousel in some cases (for different but similar uses) and it works nice. I guess it is possible to trick it to do what you need, or - better - to find an existing module that do what you want.
I know, many Drupal buzzwords, and a stiff curve to overcome, but this is the right direction in case you want to base your site on Drupal.
If you don't need all of these, and want a static page+jquery, Drupal might be an overkill altogether.