Applications don't launch - OS X won't shut down

I've started having this problem where applications won't launch. The icon just dances and nothing happens. Also, OS X won't shut down, I have to hold down the power button to shut off the computer.
The only way around the launching problem it is to reboot - on a fresh "boot" applications will launch for a while, but then it will start happening again.
If I clear caches (using Cocktail or Onyx) then it will shut down gracefully.
I really need to fix this. I recently switched over from Windows to get away from exactly this sort of thing!!
It's a pretty new MacbookPro / OS X 10.5.3
Can anyone help?

I have tried all of the above and still cannot launch many applications. This came out of the blue. From the console, I get messages like this, but disk utility reports no errors!
2008/07/25 8:54:35 PM quicklookd[165] EXCEPTION CPMessageException: (null)
2008/07/25 8:54:36 PM quicklookd[165] EXCEPTION CPMessageException: (null)
2008/07/25 8:55:36 PM kernel disk0s2: 0xe0030005 (UNDEFINED).
2008/07/25 8:56:01 PM kernel disk0s2: 0xe0030005 (UNDEFINED).
2008/07/25 8:56:02 PM ReportCrash[174] Formulating crash report for process ReportCrash[172]
2008/07/25 8:56:03 PM ReportCrash[174] Saved crashreport to /Users/btucker/Library/Logs/CrashReporter/ReportCrash2008-07-25-205601ziggy.crash using uid: 502 gid: 502, euid: 502 egid: 502
2008/07/25 8:56:03 PM com.apple.launchd[120] (com.apple.ReportCrash[172]) Exited abnormally: Bus error
2008/07/25 8:56:08 PM ReportCrash[175] Formulating crash report for process QuickTime Player[171]
2008/07/25 8:56:10 PM ReportCrash[175] Saved crashreport to /Library/Logs/CrashReporter/QuickTime Player2008-07-25-205603ziggy.crash using uid: 0 gid: 0, euid: 0 egid: 0
2008/07/25 8:56:09 PM com.apple.launchd[120] ([0x0-0x18018].com.apple.quicktimeplayer[171]) Exited abnormally: Bus error
2008/07/25 8:58:20 PM kernel disk0s2: 0xe0030005 (UNDEFINED).
2008/07/25 8:58:20 PM PubSubAgent[180] SQL Error: SQLITEIOERRREAD[10.1]: disk I/O error in "SELECT * FROM Contents WHERE rowID=?"
2008/07/25 8:58:20 PM PubSubAgent[180] <<<< ABORTED TRANSACTION
2008/07/25 8:58:20 PM PubSubAgent[180] SQLite::Exception "SQLITEIOERRREAD[10.1]: disk I/O error in "SELECT * FROM Contents WHERE rowID=?"" caught in bool PubSub::PollingFeeder::parseFeed(const Foundation::Data*, Foundation::NetError&)
2008/07/25 8:58:35 PM /Applications/Safari.app/Contents/MacOS/Safari[179] Warning: accessing obsolete X509Anchors.
2008/07/25 8:58:37 PM /Applications/Safari.app/Contents/MacOS/Safari[179] Warning: accessing obsolete X509Anchors.
2008/07/25 8:58:37 PM /usr/sbin/ocspd[182] starting
2008/07/25 8:58:40 PM /Applications/Safari.app/Contents/MacOS/Safari[179] Warning: accessing obsolete X509Anchors.

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Contributed by Fumiaki Kawashima a Level 4 here;
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