Can you fly direct to your destination if you can cruise above FL450 regardless of airways?
If ATC allows a direct-to, then yes. However, what you will file is a flight plan based on published waypoints, but not airways. So pick and choose based on great circle and trade winds and so on.


  Airways
  
  The en route airspace structure of the National Airspace
  System (NAS) consists of three strata. The first stratum low
  altitude airways in the United States can be navigated
  using NAVAIDs, have names that start with the letter V, and
  are called Victor Airways. They cover altitudes
  from approximately 1,200 feet above ground level (AGL)
  up to, but not including 18,000 feet above mean sea level
  (MSL). The second stratum high altitude airways in the
  United States all have names that start with the letter J,
  and are called Jet Routes. These routes run
  from 18,000 feet to 45,000 feet. The third stratum allows
  random operations above flight level (FL) 450. The altitude
  separating the low and high airway structure varies from
  county to country. For example, in Switzerland it is 19,500
  feet and 25,000 feet in Egypt.
  
  (FAA Instrument Procedures Handbook - En Route Operations)


And from the FAA AIM:


  Operations above FL 450 − Use aids not
  more than 200 NM apart. These aids are depicted on
  enroute high altitude charts.


compared to


  Operation off established routes from
  18,000 feet MSL to FL 450 − Use aids not more than
  260 NM apart. These aids are depicted on enroute
  high altitude charts.


and finally


  Operation above FL 450 may be conducted on
  a point-to-point basis. Navigational guidance is
  provided on an area basis utilizing those facilities
  depicted on the enroute high altitude charts.


Special RNAV points can also be used, such as the HAR, see here: What are those 5-character alphanumeric waypoints? HAR allows up to 500 NM between waypoints.

The reason for the limitation in filing a huge distance without points is the air traffic optimization. The computers are limited by how far to look ahead for conflicts is one of the reasons. I don't have numbers at the moment but I'm mentioning it in case you were wondering. Also because the different sectors and FIR's prefer to have a complete leg(s) within their own airspace. However, they can coordinate together and shoot you direct-to the destination.