Scope out all the passengers. Learn to read body language as this will clue you into the psyche of almost all people. You will then know in advance who is likely to be a safe person and which ones are questionable. This is a first good step. If possible, sit next to the person who is least threatening. Don't portray threatening body language yourself. Usually you will not find two empty seats side by side. You will have to sit beside someone and you will likely have little choice in the matter if the bus is near full. If you are in doubt at all; if it does not feel right, don't sit next to a doubtful person. Wait for the next bus.
Other ideas are to catch the "red eye" early, early morning special, so that there are few people on board which in itself is good as you can find a space of your own. If you have time, learn some passive defense tactics, like blows to sensitive spots in an attacker so that they will withdraw and think twice. You may want to google such things before you leave and get a few pointers.
Most people can't sleep on a moving vehicle, so staying awake will likely not be an issue. Most people just want to get along and are not likely to be any more of a threat than being a blabber mouth. Like yourself, they are just trying to get to their destination with as least hassle and boredom as possible.
Good luck and bon voyage!