What I currently use on XP. Ought to be the same for vista too.
Anti-virus: Avira Antivir, free edition. I switched from AVG to Avast to Antivir over the period of a few months recently. Seems to work very well. That said, I never caught any viruses even while I was using the other two. I run scans every weekend.
Anti-malware: Malwarebytes Anti Malware, and Super Antispyware. Both work nicely. I run scans every weekend.
Defragmenter: My favourite is always Diskeeper 2009. Set-and-forget and works perfectly. Unlike the above 3 programs, this one is not free.
Disk cleanup: Windows built-in or CCleaner. I've not found that much of a difference between the two, to be honest. In any case, do not use any of the registry 'cleaning' options built into Ccleaner.
HDTune. You can use this to benchmark drive performance and occasionally check up on the health of the drive. (note: NOT filesyste, but the harddrive itself).
Since you want lightweight, effective programs, I'll also recommend Opera as the web browser. It's been my primary browser for the past 8 years, and I wouldn't trade it for any other browser. Very fast, small footprint, highly customizable, and secure. Also free.
You can also try Foxit reader for a lightweight and full featured PDF reader. Less bloated than Adobe Reader.
And yeah, do not ever use any registry cleaners/optimizers!