Flight plan loaded, then during flight, i want to change destination airport...

[ThomasAH 61]

I assume both are the same here: You'll get better results (not just good) when ASN/AS16 knows where your departure and destinations are, but even without that you'll get good results, just some of the cherries on the cake might be missing, e.g.:

- wind lock

- weather info for your destination and for your route (spoken or in an FS dialog window)

- weather briefing (e.g. calculating the best cruise altitude for your route, expected runways, ...)

 

I don't know if the accuracy depends on a loaded flight plan, too, but I would expect that the highest accuracy is near the aircraft anyway and higher accuracy for other areas might only be important if you want to plan your route according to the weather, e.g. which runways to expect at your destination or alternate.

 

Speaking of alternate: This is what I would recommend to the OP. The "Flight Plan" tab has an entry "Alternate". Just enter the ICAO code there and hit "Refresh". You can (and if you want to plan with more realism: should) already do that well before take-off.