The carry on bag space on the bus will be smaller than on an airplane, so put your valuables in a small bag to carry on while your other luggage goes below. If you are taking a long trip, it will be worth your while to try to find out which buses take the fast route, and which may take a slower route with more stops. Sometimes the same line will go to a destination by more than one route, with different numbers of stops, etc. The estimated travel times are sometimes optimistic. Of course, buses are not the perfect solution for all trips.
Long bus rides on twisty mountain roads can be uncomfortable.
I prefer to fly rather than spend all day in a bus. Rental cars are very convenient if you are visiting obscure villages or ruins off the main roads. People with more time than money may want to check out the availability of buses from their city in the US to the Mexican border. Many western cities have a large emigrant population, which support frequent bus service to the border. From there, you can cross the border on foot and take an official taxi to the Mexican bus station.