Spybot - Search & Destroy is a powerful portable tool for cleaning up spyware, adware and other menaces from your PC.
The program could be used as a simple on-demand scanner. So, if you think you might be infected with something nasty, but your regular antivirus software hasn't reported anything, then check your system with Spybot - Search & Destroy and it'll give you an immediate second opinion. (Well, maybe not immediate - it's relatively slow - but this could still be very useful.)
You also get optional real-time protection, though, which monitors your system and prevents unwanted files from being installed. This isn't a substitute for a full antivirus program, but could provide a worthwhile extra layer of protection.
And Spybot - Search & Destroy also includes some interesting tools that can help knowledgeable PC users uncover all kinds of problems. So for instance there are modules to display your Winsock LSPs and startup programs, to search for Registry inconsistencies, apply a few IE tweaks, and more.
Note this is the portable version of Spybot.