One important thing to keep in mind when clicking on vanilla objects in the cells you're working in is to be careful not to actually move the object by mistake, and believe me, they are VERY easy to move and never even realize you moved something. I like to do stuff in vanilla cells too as it uses current game content as opposed to creating all new stuff. But if you accidentally move something then save your plugin, that will place what's referred to as a "dirty edit" in your mod. Many times these are not an issue because if another mod also happens to move the same object whichever mod is lowest in your load order should take precedence. However, depending on what the dirty edit does it can cause everything from no trouble at all, to causing instant CTD's which of course would not be good. When TESVEdit comes out it should provide us a nice tool to clean our mods with, and if I'm not mistaken Wyre bash can help you clean dirty edits too.
But one precaution I always try to take is to make myself a "junk" or "test" plugin that I can pull up in the CK, noodle around in whatever cell I want to to my hearts content and figure out what I want to do and the best way to do it, then edit my "real" plugin accordingly. I usually keep 2 instances of the CK open at all times, one with my junk plugin that I'm using to pick things apart, and my official plugin I plan on releasing. It's not perfect as you can still move something accidentally, but it sure helps me keep dirty edits to a minimum.
Here's a good place to read about dirty edits:
http://www.gamesas.com/topic/1356648-how-do-you-make-a-dirty-edit-and-how-do-you-fix-a-dirty-edit/
Hope that helps!
