As with any highway through a large city, stay away from it during the commute hours. This generally being 6:00am-9:00am and 3:30pm-6:30pm local time. The traffic during the rest of the day is heavy, but at least the folks on the road are not thinking about their crappy job or the mess they will face when they get home.
Anytime you can use a "beltway" or bypass to skirt the heart of a city, you should take it.
Another thought is to get some map software for your computer and use the "zoom" function to preview the complexity of the interchanges of the routes. Print out maps of the ones you plan on using, and keep them close at hand while driving. This will make your drive much more pleasant, as you will know which lane to be in before you get trapped in and exit lane or on the wrong side of the highway for your needed exit.
Some good software packages are "Microsoft Trips and Streets", "Delorme Street Atlas USA", or "Garmin Mapsource".