what everyone said: weekday is the time to go...weekend is useless due to high police presence, and slow tourists.
the BEST time to hit thin a act of frustration Gap is after 7pm (weekend or weeknight), as most tourists have headed off to their hotels and the highway patrol have left for the evening. your only concern after 7pm are the locals, who know that road like the back of their hand and go flying through at a really quick pace.
do NOT try 441 through the smokeys. it's a tourist road: slow and full of sight seeing cars. total waste of time.
the blue ridge parkway is really cool, but in all honesty, get's repetitive after awhile. AND it's also heavily patrolled by police. speed limit there is 35mph.