I have had several 250's, now have a 235 and a 350, my first v-8 in 30 years.
Both engines are highly reliable. Cost will probably be close to the same if you go with a 4 bbl, intake & headers for the 250, or buy the 350 and have to rebuild it, doing the work yourself. Truckability will be the same, but the six is different and cooler. Milage, with the proper gearing will lean to the 250, but you trade power for milage.
However, what will make the difference is the trip to Alaska. You will be able to make it with the 250, but when you gear it for milage you will struggle up the mountains. This one point would lead me to go with the 350, even as much as I love the six. I still remember our first vacation with our brand new 64. It had the 230 and 3 speed. Think it had 3.90 gears. We had a topper and a teardrop trailer, and dad went over Wolf Creek pass at 40 mph in second gear with what seemed like a mile of vehicles behind us.
