As a native Pacific Northwest-er, I would offer this advice:

Depending on your arrival time into PDX, either stay the night if you get in after say, 3pm. Use that time to check out the Pearl District or have a donut at Voodoos. I like the idea of taking Hwy 26 over to Central Oregon and going south on 97 to Crater Lake. Though an alternate would to take I-5 down to Roseburg and take Hwy 138 up the Umpqua. It is just as scenic. Enjoy your time at Crater Lake. It is beautiful. In October you will definately get cooler weather up in the higher elevations.

As for the drive up to Seattle from Portland, there isn't much. Maybe a sidetrip over to Mt St Helens and the visitor center. The key to the drive is to avoid Seattle rush hour traffic if you can. It can be horrendous. As for the advice taking Hwy 101, it is not nearly as scenic as the Oregon portion. Much of the Washington side is more inland and doesn't offer the breathtaking views of the coast.

Enjoy your trip.