Totally a style question. For myself, I went Northbound and thought it was definitely the way to go. Let me try to debunk some of the myths or at least show you the other side of the coin so you can make the decision thats right for you.
I assure you we weren't thinking about packing on our glacier viewing days ... we weren't even thinking about the end of the vacation because we still had much interior exploring to do (which is what really makes 1-way worthwhile). To the contrary, I liked the fact that things built up ... start in the Pacific Northwest with scenery that we were familiar with and watch it get progressively more stunning and along the while we're learning about Alaska (its people, history, and natural environment) before we get to the climax of the glacier viewing as a great topper.
I also didn't find the land tour tiring (certainly not more tiring than the cruise). Cruisetours tend to be too short and involve a lot of traveling compared to touring, so they can be tiring. Independent touring is actually pretty relaxing if you plan things well (very easy) and allow sufficient time (a couple of days to tour Denali as a little tack-on is where the problem starts). Don't make the mistake and you won't have the exhaustion issue.
Actually, I want the relatively easy part of the vacation to be the first couple of days. I'm always pretty tired from work those first couple of days and I definitely don't mind being pampered during that time - going to the spa, reading a book, not having to make real decisions about where to eat, etc. I do not want to begin my vacation with a long plane ride to Anchorage followed up by really long drives (5.5 minimum to Denali followed by an 8 hour driving tour of the park followed by another 5.5 back to Anchorage and than onward to board a ship). We are pretty high impact on our excursions and we get up early for deck viewing with relaxation mixed in, so for us the cruise portion wasn't (and we didn't want it to be) pure pampering and relaxation...just not our way. So, cruise portion wasn't less tiring then driving on a well-planned independent land tour with sufficient time to relax and explore.
Another advantage, I thought the structure of the cruise really helped us to tour independently in the interior -- through lectures on the ship and discussions with our guides on excursions during the cruise portion, we learned enough and developed a really great appreciation of Alaska's natural environment to do the interior more on our own. We also found that Denali was far more meaningful after all of the other experiences ... after kayaking with salmon jumping and eagles swooping, after seeing whales breaching, after seeing glaciers kalving, etc. Others seem to find the reverse true, but for me, I like to get in the small experiential things that build up to the big highlight.
Our cruise experience was in large part set in stone because we booked our excursions in advance (as you'll want to do to get the best excursions). The land tour was more free form. We knew a bunch of alternatives in each of our destinations and along the way, so we could pick and choose once we were there. After the fixed cruise portion, we could better guage the land experience we wanted - did we want more native culture or more nature/wildlife or more museums, did we want more physical activity or something more relaxing, did we need to do some more shopping, etc. It just led us to have a more well-rounded and enjoyable vacation because we could adapt the land portion in a way that we could never adapt the cruise portion. I know how I vacation, and if I went Southbound my first time, I probably would have been trying to do too much on the land tour even though they were experiences I could deemphasize after having experienced the cruise portion.
Issues in favor of southbound are cruising Vancouver during the day and not having to bear the long flight from Alaska at the end of your vacation. You'll have to weigh the pros and cons for yourself.