Alaska definitely cancels flights for operational reasons. In the advent of a cancellation, I believe that AS is generally pretty good about re-booking passengers on the next available flight, even if its with another carrier.
At any rate, I'm sure they wouldn't cancel a flight purely because of a low passenger load. However, if there is a mechanical concern or problem with an aircraft and no spares are readily available, they may "find a replacement plane" by way of canceling a lightly booked flight assigned to the same aircraft-type. Likewise, if for some reason a flight crew is unavailable/incomplete, it stands to reason that emptier flights are more likely to be cancelled. Also, keep in mind that AS, like many other carriers, has prioritized certain flights that consist of more than one segment and/or often carry a large number of connecting passengers. They will do whatever they can not to delay or cancel these flights.
In short, the flights most likely to be cancelled are lightly booked, single-segment flights on routes with a high schedule frequency.
I'm sure flight ops will do their best to avoid cancelling the last flight of the day, but it has been known to happen before.