Further to coob's answer, I find adding these directories to Spotlight's ignore list (System Preferences → Spotlight → Privacy) helps:
~/Library/Developer/Xcode/DerivedData/
(Xcode 4 build artefacts)
~/Library/Application Support/iPhone Simulator/
(file system for the iPhone Simulator)
Like this:
(See this blog post for additional detail.)
Update: from a comment by joerick: "This works, but it also meant that Instruments.app couldn't find the debug symbols, so I had to remove DerivedData from the Privacy list to do some profiling." - bear this in mind if you use Instruments.
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