We just completed the one way from Seward to Vancouver. That added more logistical challenges, and it's expensive to get between Seward and Anchorage. It sounds like you're already thinking about that, but be sure to price it out. I think Seward to Anchorage is a little easier because there are more tour options. We took a rental car for $320 since we had 4 people. Also the added cost for flights, probably a hotel in Anchorage, etc. We had our teenagers with us, so in hindsight I may have done the round trip to make things cheaper and easier, but with just my husband and me, I'd probably still do the one way.
I loved the drive between Seward and Anchorage. It's beautiful. I also liked getting to see more of Alaska, even for just a few hours.
I would've hated to miss Skagway. I'd say that's your biggest negative on the round trip itinerary. The town still looks historic, so it's very unique, and there are some incredible shore excursion options there. We did dog sledding and loved it.