Upvote:9
The Tomei expressway (main route between Tokyo and Osaka) will be very crowded at both ends of Golden week in the appropriate direction. Far less at nighttime, and about average mid-week. I assume you have made all your reservations already? GW (this year) has basically begun already, which has the side effect of spreading out the travel.
Of course, one minor accident can easily produce a 30km traffic jam that will take 4-6 hours to clear.
Train travel is more reliable, of course more expensive. A Shinkansen from Tokyo to Shin-Osaka is $150, regular fares about half that but the travel time is over 8 hours. Again, if you haven't reserved a ticket by now you will be standing the entire time, but that's only 2.5 hours.