1). Intonation is usually adjustable.
2). Nuts can be replaced
3). Single coil pole peices are often stagard, so if you have good ears their is an audable difference. This isn't even getting into coil windings, hum cancelation/ no longer canceled...

But yes, if you choose to play a guitar left handed, you're going to run into some real problems. That's why it's probably better to just play right handed. After all, the guy who invented the format that Guitars, Mandolines, Lutes, etc on back take wasn't left handed and everybody just assumed that's the way it's supposed to be? Maybe what we consider a "right handed" guitar really is a left handed one.