Open Console in Utilities & see if there are any clues or repeating messages when this happens.
Bootup holding CMD+r, or the Option/alt key to boot from the Restore partition & use Disk Utility from there to Repair the Disk, then Repair Permissions.
If that doesn't help Reinstall the OS.
The problem #1 :
If I just using image Preview one picture. I can close or quit when using short cut command r / command q.
The problem #2 :
If open 2 pictures file by image Preview. the window's grey color . . . sometime is normal with Blue Browser (I can use down button and using short cut command r / command q.
BUT sometime is a bit of Lt. grey. with grey browser (I can't use any button or short cut in this moment.) I must use cursor click many many time till Lt. Grey to Normal Grey, or let the file name had Blue browser.
p.s. the OS X ver. ~ lastest ver. 10.8.2