The safest seat is in the middle, in an aisle seat on the side opposite of oncoming traffic (this depends on country UK/US).
The front of the bus is vulnerable in a head-on collision. The rear of the bus is vulnerable in a rear-end collision. Passengers in the middle on the same side of oncoming traffic run the risk of a collision with an oncoming vehicle or something like a ladder running amok and shattering their window.
In terms of comfort, the front is vulnerable to the yelling or loud music of the drive, while the rear is vulnerable to the smells of the bathroom. The middle wins again in terms of comfort.
Read more detail before you choose a seat on your next trip. Nothing worse than being decapitated en route!