I generally will always take the interstate or four lane roads.
I think it is safer...less chance of a head-on collision, I'm not blocking traffic and I can pass those who are blocking traffic.
The on ramps allow others to merge as opposed to people pulling out from their driveways, etc.
In case of engine or tire problems I can get off the road far enough for others to pass by me.
As time goes on I see more and more people texting and not paying attention to their driving...hence I want to give myself every bit of an edge to get out of their way.
So, my answer is...stay with the four lanes. For those who claim the scenery is bad on a four lane...I disagree. I've hit all the lower 48 states and found beauty everywhere we've gone.