I hop out, go in the store, when I come back and attempt to start the car my key won't turn in the ignition. Main fob key (the one I've always used) won't work but my secondary key will. Anyone experience this before?

 

Keep an eye on the PATS security led light on the dash. If it rapidly starts to blink when you turn the key then odds are that the transponder chip in your key is no longer functioning and activates the immobilizer. Had this issue happen to me recently on my 04 XJR and had to have new keys programed

 

Or if it doesn't go out, then it's not even seeing the key turn (bad lock?).

Start now by watching what it does when all is OK so you'll see what has changed.