personally i wouldn't have it on if i was handling approval with nintex workflow.  but you can use request approval in worklow and use the set approval status action which updates the built-in SharePoint approval status column.

if you turn it off then how would you want your workflow to be started?  on item creation?  on item modification?  manually?

If you do not turn on content approval, how in your experience do you start the workflow, I assume each situation may be different, but just wanted to make sure I was not missing anything...

I would normally have a workflow that has a conditional start where status = Submitted or similar.

I have also had times where it is a manually started workflow from the item context menu.