As far as registration goes you're going to have to deal with your own state and do your own research. Every state is going to be different. I can, however, give you an example of what you're going to deal with in Minnesota as your state will likely be similar.
Driver:
You're going to need a Class C license to carry more than 15 passengers. If you have air brakes you are going to need that endorsement. Furthermore, you're going to need a passenger endorsement. The Class C allows you to drive a vehicle capable of carrying more than 16 people total (driver included). The passenger endorsement allows you to drive it with those people actually on board. Makes sense, right?
Part of the process is going to include getting a medical certification in addition to passing the written and practical CDL tests.
As far as the bus...
In Minnesota you would need to register it at 26,000 lbs or less and not exceed that weight in order to get away with the Class C instead of Class B license. You also will not be able to have a trailer that causes the total combined weight of the bus and trailer to exceed 26,000 lbs.
The bus will need an initial inspection and most likely would require a "reconstructed title" in this state. That is different from a salvage title which is generally a negative thing. Technically, swapping to Dana 60's under a pickup that originally had Dana 44 axles would require the same thing. It is not expensive, but passing as a commercial vehicle might be more difficult (seatbelts and the like). You will need a stack of receipts.
The bus will also be subject to highway patrol inspections every year as well as the normal commercial vehicle requirements (displaying DOT number, for example).
As far as plates go in this state it would likely get BY plates which are bus plates for anything that is not municipal. They are weight based.
Insurance is going to be a chore. Commercial insurance is NOT going to be cheap and I'm sure you're going to need a rider about liability pertaining to your own passengers. Research with your agent.
The last thing to keep in mind is that everything will need to be legal. For example, in this state an open bottle is an open bottle. Your passengers would not be able to have an open drink even if there was a divider (common misconception). However, an RV is allowed to have an open bottle of booze so long as it isn't accessible by the driver. Being in a cabinet, for example, would pass. Yeah, it's a gray area.
Best of luck and let us know what you find out.