Given that this is a '1 thing' question, I would have a hard time choosing between:
1.) A better Finder. Not even sure if that would be just one thing by itself, since there are so many things the Finder could stand improvements on.
For example, I would like to see the search field act as a sort of 'find as you type' in the same way that iTunes does (I would use this so much isn't funny).
Smart folders themselves are a nice idea, but there's something off about the options. For example, the other night my girlfriend wanted to search a folder she has for all mp3's below a certain bitrate. It took us a while to realize that to limit the search to a particular folder, we had to navigate to that folder, then start typing in the search box, and THEN we could select this one folder to base our search on. Well, life would have been easier for me that day and several since if I could just select the folder right after hitting option-cmd-n, but I can't. Smart folders are such a nice idea, but I don't use them as often as I would simply because the process of making them isn't as streamlined as it could (should) be.
The above situation could also have been helped somewhat if OS X showed bitrate beneath the filename as it does image size for jpgs and such. And helped even more if we could sort by something other than filname, etc, that we have now.
And an actual 'cut' option would be fantastic. They could even call it something that wouldn't sound like it came from Windows, like 'Pick up' or whatever. Because then it would be sooo different. And maybe Apple fans would finally embrace it.
As far as an actual path is concerned, I rather like the implementation of it now, what with the drag and drop and all, but how great would it be to be able to edit each little part of the path? Or to be able to highlight parts of the path like regular text so they can be edited or copied? If there was a hotkey to jump straight to a path with this feature, Finder would already be so much better. When the path is too long to fit, some sort of magnification (not quite as egregious as the Dock's, but something) would help get where you need to go.
Ability to restore items individually from the Trash. I've accidentally thrown files in there and not realized it until after I closed the Finder window I was using, so putting them back involves navigating back to where I was and then opening the Trash and dragging them back. And as with 'Cut,' if 'Restore' sounds too Windows-like, I'm sure Apple could think of something else to call it - like 'Put this back' - they have smart people who can think of catchy things like that.
The ability to have every single button in a save dialog (and maybe the entire OS while we're at it) accessible from the keyboard would remove a hassle that's always bothered me.
And I know there are many here (most likely those who dislike the 'cut' and 'restore options) who will also hate this next idea, but I would like to be able to expand items I put in my sidebar to see subfolders. We already have similar ability in iTunes with playlist folders, so I don't think people would be overly confused, which seems to be the usual argument against putting anything useful in Finder or OS X in general.
2.) A better Dock. Again, I don't know if it's one thing, since there's a lot I would like to see done to it. I like the Dock, actually, though it took me a while. Even so, 4 years ago I had some nice ideas I wanted to develop into a replacement Dock, but since I did not have the time or know-how, I sent on these next ideas as feature requests. Unfortunately, it seems that several of them have been put into Windows 7's dock (or whatever they want to call it - it's a dock nonetheless), so I doubt we'll ever see them on OS X, which makes me sad on the inside.
I've never really understood the reasoning behind having the two sections in the dock. Why windows don't minimize behind their program icon I don't know, but they should. Especially if hovering over or clicking on the icon would show a little display of the minimized windows - something the Stacks grid or fan views, I guess, though I had something a little different in mind originally (like Exposé on just those particular minimized windows). I doubt we'll see this ever now that it's going into Windows, though.
Stacks working like it was originally shown to us would be awesome.
Not sure if this is a Dock feature or what, but I know many of us would like to have different Docks in different Spaces. Whole different desktops would be nice, but even if it was just the Dock alone, that would help me out.
So yeah, either a better Finder or a better Dock. And now I will quit bothering everyone.