The General Manager is the person who oversees all hotel operations. The Rooms, Food and Beverage, and all back office functions (Accounting, Sales, Engineering) report ultimately to the General Manager.
Sometimes the title Manager is an abbreviation for Front Office Manager or Rooms Division Manager. This person is responsible for the Front Desk and Reservations and possibly Housekeeping. Manager can also be applied to a person responsible for the hotel while the General Manager is away. Usually, on weekends, a hotel Manager will oversee operations while the General Manager is off.
In larger hotels, Manager may be a permanent position - one step below the General Manager. In smaller hotels, the weekend Manager is a position that rotates by week among Department heads.