Removal of all markup and overall customization
you can customize drupal as deeply and drastically as you please. typically that requires more intimate knowledge of how drupal works.

For alot of field based modifications the Display Suite module allows per-field HTML Reset to customize the HTML outputted per field. A lighter weight approach to the same idea of "resetting" how drupal outputs a field is the Fences module.

With regards to JS there is hook_js_alter which you may use the remove/alter what javascript files are loaded on the page.

All the HTML for the page can be tweaked from the html.tpl.php file used by your installed theme (or the base core supplied html.tpl file).

Have I done allll of these?! No, but I have used hook_js_alter to conditionally include JS on some pages via a module. I have for example removed all sidebars and unset I think most of the CSS found in &lt;head&gt; by conditionally supplying my own template file to a menu path via hook_menu:

Load custom template from MENU_CALLBACK

So there are tons of utilities to do this in Drupal. How these utilities play with 3rd party modules you want to leverage on your site ... or just how much custom work you want to do on your own website -- I leave as an exercise for you.