This is what I have been using for a few years now and it works just great.
1) Spywareblaster the first line of defense...the program stops things before it gets loaded into your system
SpywareBlaster
2) spybot S&D this is one of 4 intermediate layers
The home of Spybot-S&D!
3) adawareSE What spybot doesn't catch this one will.
Lavasoft
4) Ccleaner This one will help the other two out plus has a registry cleaner
CCleaner.com
5) winpatrol Scotty the watchdog will tell you when there is something trying to get into your registry and will also act as a start folder cleaner to stop those unwanted programs from starting up plus a few other goodies
BillP Studios: WinPatrol
6) my latest ptogram to be used within my system is ewido which is now AVG antispyware.
ewido - anti-spyware and anti-malware solutions
These all work extremely well with each other and are clean with no add-ons or the likes (ccleaner has yahoo toolbar which can be unchecked)