I-5 is the quickest route. US 101 is probably the most beautiful route, but it's twice as long to take. The other option is US-97 that takes you past Crater Lake through the High Desert and Bend.
If you have the four to five days it'll take, I would unhesitatingly go 101. I've driven it all the way from LA to Aberdeen multiple times and love every moment of it. You'll want to stop every where:
San Simeon and Hearst Castle: http://www.hamell.net/hearst-castle/
Humboldt Lagoon: http://www.1nova.com/photoblog/2011/12/17/humboldt-lagoons-state-park/
Eureka (good place to stay the night,) Florence, Newport Bay: , Depoe Bay, Boiler Bay: http://www.1nova.com/photoblog/tag/boiler-bay/ , Neskowin: http://www.1nova.com/photoblog/2012/11/11/neskowin-oregon-ghost-forest/ , Tillamook: http://www.1nova.com/photoblog/tag/tillamook/ , Cannon Beach, Seaside, Astoria: http://www.1nova.com/photoblog/tag/astoria/ . And about a dozen other locations that I didn't mention, many of which could use an entire day to explore by themselves.
If you go I-5 you have some good options such as two ghost towns: Buncom: http://www.1nova.com/photoblog/2012/06/13/ghost-town-buncom-oregon/ and Golden: http://www.1nova.com/photoblog/2012/05/27/golden-oregon-the-driest-ghost-town-in-oregon/ Mt. Shasta area then of course towns like Ashland, Eugene, Salem and Portland.
To get to I-97 you'll take the turn off from weed at I-5. The drive to Klamath Falls is really nice, north of there you can stop off at Crater Lake: http://www.1nova.com/photoblog/2010/10/11/crater-lake-oregon/ and Bend, detour to Fort Rock: http://www.1nova.com/photoblog/2008/09/27/fort-rock-oregon/ go over Mt. Hood and loop back into Portland to meet I-5 again. This will be only about 150 miles longer then going up I-5 so if you have limited time that might be a better route. For my money it's more scenic then the I-5 route.
Keep in mind that all three routes have different climate zones too. 101 is very much an Coastal Climate, windy, rainy depending on the time of the year, very twisty roads in places. It's more crowded due to tourists in the Summer, and will be much harder to find a place to stay.
I-5 is the straight shot up the Willamette Valley. Greener, more rainy in the fall/winter/spring, but more diversity in plants. Less reason to get off the highway unless you want to explore specific cities.
I-97 is Oregon's High Desert. It's totally different then anything else you've probably experienced. Winters can be cold with snow, summers are warmer on average then the rest of Oregon. Much less rain then the other two area. Less vegetation diversity and fewer towns to stop at. But it's still an attractive area to drive through and spend some time in.