How many pilots are required in an Airbus A380?
In general, it is perfectly possible for a single person to fly modern aircraft like A380. However, regulations require the presence of 2 pilots (PF and PNF). In other words, technically yes, legally no.

In long distance flights, the aircraft usually carries two sets of cockpit crew (4, each capable of flying the aircraft) as the flight hours may be more than the permitted flying hours.



FAA Advisory Circular 25.1523-1 deals with the minimum flight crew in transport category aircraft. According to Section 5 Certification Procedures, Subsection c, Testing (vi) Incapacitated Crew member,


  Whenever the applicable operating rule requires a minimum flightcrew of at least two pilots, the certification program should include a demonstration
  of operations during the total incapacitation of a crewmember at any point in a given flight. It must be shown that the airplane can be operated safely and landed safely with the remaining crew at a planned or unplanned destination.