This Apple forums discussion post describes an error that many iTunes 8 users are getting:
"iTunes 8.0 gathers data about my music library well enough and sends it to Apple too; but then 10-15 seconds into 'processing' by Apple, iTunes stops and reports that 'Genius results can't be updated right now. An unknown error occurred (4010)'. I thought it might be overloaded servers and tried several more times in the hope of squeezing my request in between those of everyone else; but that didn't work; plus if it were a server issue I'd expect to see postings here from others with the same problems, and I'm not."
Several posters have tried removing dead tracks--tracks whose files cannot be located as designated with the encircled exclamation point--from the library using the script Super Remove Dead Tracks and trying again, and although this didn't work for everybody, several posters did get things working correctly afterwards.