I've inherited an older Dell 2650 for use at home and I don't really have a place to put it where it is oriented correctly. Is there any risk in running the machine while on its side?

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No, you can safely run any*) computer in any orientation.

The only possible concern would be heat dissipation. (That, and the CD falling out of the tray if it's upside down.) Machines are normally constructed to take advantage of the fact that heat rises, but most normal machines don't generate enough heat for this to be a significant problem.

*) The only exception might be really high-end machines that generate lots of heat. For these, heat dissipation is a major issue. Additionally, they may be water-cooled and who knows where the liquids flow if you turn it upside down :-)
(Water-cooling are closed systems, but they might not work properly.)

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although make sure that all air intake and exhaust vents/ports are clear and unobstructed. – Xantec Nov 24 '10 at 19:09
Always a good point! – Torben Gundtofte-Bruun Nov 24 '10 at 21:41
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There is a slightly increased chance of disk drive problems, such as seized/stuck bearings if the drives have been run in one orientation for a long time and then find themselves lying another way. This is due to the wear pattern on the drive bearings.

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