As a troubleshooting step, tune the G string around 10 cents flat and see how it sounds. How 'bout 10 cents sharp?

How is the action set? The strings will be higher above the fretboard the higher up the neck you play. If the action is high, you could be pulling the strings out of tune by simply playing.

What gauge strings are you using? 9s and lighter can easily be made to sound sour by fretting with excessive pressure. Try playing with a lighter touch, or try 10s.

Make sure the pickups aren't too high. I've had weird intonation problems from having a bridge pickup to close to the strings on a Strat.

Check for loose hardware. A buzz somewhere in the G string hardware could be making it sound wonky.

Some people are really sensitive to the compromises in equal temperament tuning. Maybe you're one of them.