In previous versions of Safari, one could right click on a PDF being viewed in Safari and there was an option to 'Open with Preview.' In version 5.1, this functionality had seemingly disappeared.
I searched the web to see if I could find an answer to restoring the pre-5.1 behavior, but couldn't find anything. Fortunately, I stumbled upon the answer by accident: In the new version, to have that option enabled in the contextual menu, you have to have something selected. So if you're viewing a PDF and want it opened in Preview instead of Safari, just hit Cmd+A or 'Select All' from the Edit menu, now right-clicking shows you the 'Open with Preview' option again.
Why Apple changed this, I don't know, but I find it bizarre and arbitrary because this action that used to take a mouse click and movement to perform now takes a key combination plus a mouse click and movement.
But I find most of my time spent screwing around with computers these days is spent trying to restore functionality that used to be efficient and rapid, but has changed with a software update to be less so.
[crarko adds: I tested this, and it works as described. It is annoying when functionality disappears (or is hidden) for no apparent reason.]
Mac OS X Hints