My 2 cents...
As a field engineer that sees this stuff everyday, Pestpatrol does the most thorough job. I have only been using it a few weeks, but I have had the opportunity to test THROROUGHLY.
I have used Spybot, Ad-Aware, Spysweeper, Norton Antivirus, McAfee, and I ALWAYS, not sometimes, ALWAYS find MULTIPLE items that these other programs miss, even when they have the latest definitions/updates. I'm not talking about a few cookies either, but usually executables, library files, and registry keys that the others miss completely.
Conversely, if I use say Ad-Aware or Spysweeper after Pestpatrol, I'll find only a few things left behind, and these are usually cookies or on occasion, a registry entry or two. I liked Spysweeper, but I have trouble running it in safe mode (the display is often too large to click on things to see what you are doing), and it often fails to load on XP, with software list errors. They even mailed me a new build, didn't help.
Bottom line, PestPatrol does the best job of any of the tools. To be thorough, when cleaning spyware, I recommend using at least 2 tools. I use PestPatrol and then Ad-Aware.
If your desktops are over a 1ghz processor, and run antivirus, I haven't seen a noticeable slowdown, and users have not complained to me yet about their applications being slow. Seems to operate well on a day to day basis. My once favorite tool Spybot misses A LOT OF THINGS NOW!
For corporate environments, I would use the PestPatrol Product for defense, and not rely on your Antivirus to do an adequate job. I've seen lots of machines running Norton 2004, covered with active spywares/adwares.
Matt J.
Please always take the time to backup any and all data before performing any actions suggested for ANY problem, regardless of how minor a change it might seem. Also test the backup to make sure it is intact.