Whether a site is generally safe or not is only part of the issue. A hacker can get in to most sites and stick in a malicious payload.
Make sure that your Anti-Virus software is up to date and is set to scan all files being downloaded. Also, make sure it is set to scan the contents of archive (ZIP) files.
Another thing to keep in mind is that some system utilities look like a virus because of what they can do.
Sites that I download from include:
Microsoft Marketplace
http://www.windowsmarketplace.com/?WT.mc_id=1106_05
I see that they have split the market place into 3 general categories, Windows, Office, and Tech.
www.download.com
www.snapfiles.com
www.nonags.com
Some sites link to Tucows which has been around a long time.
If you like Hewlett Packard RPN logic calculators, check out www.hpcalc.org and www.hpmuseum.org
Even for sites you trust, it is not a bad idea to manually scan the downloads for viruses before you install the software.
Chas