"John Cunningham may have 'hopped' the first comet - I wouldn't fancy being the poor so-&-so who has to flight test the first A380!"
Noisy,
Nowadays most aircraft have been "flown" in the simulator for many hours before the first flight of the hardware. For FBW aircraft like the A380, the characteristics will have been deliberately tuned to be as close to that of the rest of the Airbus range as possible.
There are also aircraft that can be set up to simulate the handling of much larger types - examples of which are the Calspan Learjet and Bombardier's ACT Challenger (A/C 3991). Crews also will fly similar aircraft if they're available.
Even without these facilities, the usual work-up is low speed taxi, high speed taxi (both with full systems checkout including Electro-Magnetic Compatibility) and then, finally, first flight.
P.S. Weighing to verify the C.G. is one of the most common flight test procedures plus most flight test aircraft have a water ballast system (two tanks at either end of the cabin). This allows the FTE to set the CG to the precise test requirement