I have a 200 gig Maxtor drive set up as an external USB drive. For months it ran cool for hours--getting just barely warm to the touch, even while I worked on video files kept there. Now, it seems to start heating up immediately, even when nothing should be accessing it, and it's gotten warm enough within 30 minutes I've shut it down.

I've scanned it with several anti-malware programs, and the scans all came back negative. (It's not the fan, because the enclosure doesn't have one.)

The drive has been 75-90% full pretty much since day one. Anyone have any thoughts what could've caused this change?

Because there is most of enclosure that doesnt provide the adquedate air flow. so that happens the heat. You should buy the enclosure with fan combo that will ease the pain in your hard drive. If you still using it, the hard drive will fail shortly.