Seriously, for real long distance or hard to reach destinations, fly if possible and you can get around when you are there (rental car or trains).
For a vacation it is awful that you have to spend a large number of days just to get there and more coming back. For shorter trips or when it is better to have your own transportation when you arrive, I never mind a long drive and having my car with me. 10+ hour drives don't bother me at all and cost wise don't make a difference either.
Not entirely sure any method works best. I suppose if you bus; train; boat; plane you don't have the worry of worrying about other vehicles so much. But of course, it doesn't give you much choice. Especially if you need to use other forms of transport to make connections between the two ! Car I suppose is probably easiest in that you get to choose when you go; when you stop; detour if you want. But then you're subject to everybody else's stupidity !
