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Btw, it's safe to open while running, right?
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Yes it is safe to turn it on while it's open. Obviously you never want to unplug or remove anything with it turned on. Avoid touching it or breathing on it because of static form your hands and moisture from your breath can hurt things.
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I'd hear a high-pitched whine from the tower.
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If the sound wasn't always there I'd bet it was a fan that was failing. This may or may not be the cause of the problem.
To troubleshoot your problem:
1) Run a virusscan make sure you don't have like MSBlast or something (though it should be really obvious if you did).
2) Check the case and processor tempatures with motherboard monitor. If the heat is high check the fans and make sure the heatsink is affixed properly.
3) If there is no overheating, replace the powersupply with a new good quality 350-400W PSU.
4) If the problem occours with no overheating and a new PSU does not solve it then test the motherboard and RAM in another computer.
My best guess is that it's a failing PSU since the computer is like 3 years old. Those things wear out over time and if it's a commercial DELL box you know they've got a cheap underpowered one in there to begin with.