I think the easiest way to tell might be to inspect the cables. It's near impossible to re-wind cables the way they were in the box, and after being in the box for nearly 20 years, there should be indentations on the cables from the twisty ties. If they don't look like they've been setting that way for a long time, that'd be fishy.
Regarding the console itself, I'd primarily look for dust in the cracks and finger prints around the open button. That stuff is hard to get perfect with just a wipe-down. If you can, you can also open the console and look to see if there's even a faint amount of dust around the hinge gears. That area also gets a little bit of dust with use, even in clean environments, and is really tough to clean without taking the unit apart and giving it a bath.
If it's suppose to be in an unopened box, then inspect the creases where you open it. The corners might have wear from having been moved around and possibly bumped, but that fold should be pretty clean and crisp. If it looks like it's been open a few times then, well, it could be new but it's not "unopened", that's for sure.
RH's post in How can you tell if a Gamecube System is Brand New? Unused? was marked as the answer