I have also have this problem. I too am running Preview on a MacBook Pro with 16GB ram. It is a slug. It ran fine on OS Lion. Since updating to Mavericks, it appears something changed. I now notice a blue drop down box flashing down and up, hard to read. It locks up preview and will not allow viewing or allow me to quit Preview. It appears to be trying to index images on any memory card plugged into the Mac.
I can no longer quickly inspect memory cards for contents before deciding whether to delete the contents. I also have Sony format raw and jpeg images, and all Apple updates to date.
I have resorted to using Force Quiit to get out of Preview which, with Mavericks, seems to be extremely flawed (unless this is another attempt to eliminate privacy by collecting everything ever loaded on a computer, in which case you can report to the NSA it is working fine....).
Serously, I hope someone at Apple is monitoring this and will correct what is likely a HUGE conflict between Mavericks and Preview. This is bad for Apple's reputation, as I and others will be sharing this experience with others who have a right to know there is an unresolved problem. This has wasted several hours of my time trying to find out if it was something I had done. Apparently not, as others are also dealing with this issue.