I generally enjoy driving. On long trips, I have a rough limit of about ten hours drive time per day in a car, and aim for a little less in my motorhome as it's a little more exhausting to drive. How late one can reasonably arrive at a campground without causing undue annoyance (and how early one can leave in the morning) is sometimes another limitation. This works out to maybe 400-450 miles or so on the highway.
Different people have very different ideas about how to travel, of course. There are some people here who wouldn't go more than three hours if they could in any way avoid it. There's nothing wrong with that, of course, and it can be a great relaxing way to see the country, but on the flip side it does take more time...and not everyone has large spans of time available for travel.
Road conditions can play a huge role in how comfortable the driving is. Six hours in heavy rain or snowy conditions is much tougher than more time in fine weather. Unfortunately, it's not generally possible to know the local weather you'll encounter when you're planning out a long trip in advance.
It may help you planning to try a somewhat longish drive in the RV you'll be using, if that's a possibility. An hour or two behind the wheel might give you a better feel for how comfortable you'll be on the road.