I am looking at renting a vehicle from downtown Seattle Washington and driving to Mission BC, Canada, is this something that can be done?

Of course! Hertz is the best rental car company for travelling to Canada because there is unlimited mileage!

Yes. I did that several times this summer, but I returned it to the downtown location. I think there is some kind of warning online about insurance working differently in BC.

Yes. You can pickup and drop anywhere as long as they have service in the drip off location