www.malwarebytes.com for any and all things spyware. Free. I Install it on every house call computer I have. mayer said it, make sure the hard drive has AT LEAST 10% free space, the more the better. schedule disk cleanup and disk defragmenter to run frequently at off hours. RAM. Can't have enough of it. Too cost effective to not consider. At least 2 Gb. I always used to see how many windows of office docs, system tray apps and web browser windows a person has open. The user can usually be the culprit to a lot of "its sooooo slow" problems. Restart the computer in the morning before starting to use it. Did I say RAM?
Didn't realize the separate I/O board was present. It could well be the connections from the I/O board to the logic board. This is one of those issues that just isn't going to be fun to diagnose. Its not very clear if its the I/O board or the logic board at this point. Here is the link, the ribbon I speak of is shown in step 27: Click here. Clean connections if there is any residue on anything. Reseat the ribbon on both ends if possible. I once came acrossed a laptop with a keyboard issue (most keys typed correctly, some would type two different keys). I replaced the keyboard only to see the same issue. So I opened it up again, cleaned the ribbon and ribbon slot for the OLD keyboard (with a very small torx pointy bit) and all the keys worked again. Good luck!
If you have the same issue as that one, then you either need a new logic board or can use USB-equipped speakers to bypass the issues. The USB speakers would probably be the cheaper alternative. You can start looking for USB speakers that are compatible with a mac (double check!) HERE.
You might check the HDD cabling to look for anything out of the ordinary. I once put a new disc drive into an iBook G4 14" only to find (after it was put back together) that it wasn't the drive, it was the drive ribbon (it appeared that a small screw had slightly punctured the ribbon.) I replaced this for about 12 bucks. I hope kkirch's comments did the trick for your sake :-)
Try resetting the PMU. A quick search with google should send you to apple's website with the directions. If that doesn't work.... Either your OS install has gone pooh city or the logic board isn't in good shape. Do the USB devices show up in system profiler? If they don't but your mice and such do, try booting off your Mac OS X install cd or dvd and check system profiler from there to see if your storage devices are detected that way. If they are detected when booting up off of the install media, its your OS. (possibly your user account? Try creating a new account and see if things work under the new account before reinstalling your OS.)