Remove real player, wmp7/8/9/10 (not the codecs.. just the program), MMJ, kazaa or any other bloatware...
Unles syou install lots of bloatware the registry shouldnt be too bad.. Ive never bothered cleaning it..
See what programs are running at startup. Remove things like Realplayer, Msoffice, quicktime etc.. - which all add themselves to startup each time they are run.
Also if your drives are fat32 run defrag every week.. for ntfs you dont really need to bother, although it will help a bit.. but I havent done mine for about a year
Also remove any software firewall, and get a hardware firewall from ebuyer for ~£10-15. Use a portscan site to check its working good...
Antivirus does not need to scan in real time, so disable that, but do a full scan every week or so. Making sure software is upto date and resonably secure is more important
imo (most people seem to forget or not bother).