How to keep Windows running smoothly (compared to other Windows, not compared to OS X or Linux).
The Holy Trinity (if you don't have these, get them now):
Ad-Aware: Click Download (on the right-hand side, last time I checked) not Purchase (at the bottom). This was the first quality anti-malware program.
Spybot (Search & Destroy): In my opinion, now better than Ad-Aware (although I do run both). Also, ONLY free, no pay version (although you can donate), so no lame attempts to get you to click Purchase.
SpywareBlaster: Another quality freeware program, this one isn't like the previous two. SpywareBlaster prevents (among other things) some (many) spyware programs from using browser exploits to install themselves on your system.
While we're on the subject, switch to Firefox. The only 100% effective way to prevent IE browser exploits is to abstain from using the IE browser.
Additionally, there's also Microsoft's Antispyware (beta). It's still a bit slow and cumbersome (but...it's from Microsoft), so I don't use it, but every little bit helps.
Also, make sure you have a firewall running. Windows comes with a firewall, turn it on. Alternatively, you can use a separate firewall, like Zone Alarm. I think Zone Alarm is probably the best firewall program at the moment (but it's not perfect), although I cannot recommend the cheesy "free" (crippled) version. If you want free, just use the Windows one.
Finally, make sure you are using a good Anti-Virus program. Norton AV used to be my top pick, and if you hunt you may still be able to find it bundled with Norton System Works (which I still recommend, but that's Off-Topic) free after rebate. At the moment, though, I think Norton AV has grown bloated and slow, so I currently recommend Grisoft's AVG. Get the free version, the engine is the same as the pay version. Yes, it will run every night and you can't change that (except the time), but it will also update every night, and it's FAST (compared to Norton) and caught several viruses that Norton missed on my computer (both with latest updates).