Something i often do when i have the luxury of getting into a relatively empty bus is get a window seat on the curb side. This way it's somewhat easier to see if someone walks off with your shit when you're at a stop.
Other standard travel tips apply: having a shitty/beat-up bag works in your favor because it doesn't look worth the effort to steal, have something unique on your bag so other people won't mix it up with theirs, and bring valuables (passport, money, electronics) to your seat in a small sack.
If you can swing it, it might be better to get on the bus outside of the main terminal so that you can see the driver put the bag into the bus yourself. In North America, the downtown bus terminals tend to be pretty sketchy anyways, so it might be less stressful to just wait at a gas station or shopping mall in the burbs. On the other hand, you often then also give up your chance for a good seat.