I generally leave it on most popular over the past 24 hours. I occasionally set it to new art for a bit because there are a lot of awesome pieces created that never become popular. However, I always end up becoming frustrated with it because it seems like so much of the new art is screen caps/clearly stolen art/recolors/etc.
I have newest turned on so I can offer comments and faves to newly posted art that I like. I know how much it sucks to have art that no one really pays attention to, and how exciting it can be for someone I don't know to comment on a work I've done.
I haven't visited the main page since version... I don't know... 2.0?
I've set my DA tab on my browser to hop right to my profile so that I can avoid the bull crap of the front page while checking my messages. I also "browse" by skipping along friends-of-friends and favorites-of-watches, etc., and have an endless stream of new faces and styles in the genre I like because of it.