Great points so far. I probably drive exactly like your wife....very conservative and extra cautious.
We started with small Class C's which I was afraid to drive (although I did a little). Somehow when we got our first Class A, which I thought was so huge (only 28'), I started driving. I actually thought it was easier to drive than the Class C due to the whole side of the MH being even (i.e. behind the driver not wider than the cab). Then I was scared of getting a tow car. But we did. And I've lived to tell about it. Now I do all the driving. The main things that concern me are merging into traffic, and pulling in and out of gas stations. Like others, I try to avoid traffic as much as possible. But I've driven through Seattle, parts of L.A., etc. Yes, I'm still nervous, but it will pass. For gas stops, I try to look up the stations on Google maps satellite/street view ahead of time. That helps alot to choose one that is easy in/out.
On another note.....How much traveling/camping do you do? Maybe you could just rent a car sometimes at your destinations? Some people prefer to do that.
The more miles driven, the more comfortable she will be. Probably the same that happened when she started driving the MH.