Don't know about you, but I'd much prefer never to get the spyware in the first place, rather than worry about how to get rid of it once I have it.
So I follow a set of very simple rules that keeps my system free of this garbage. They aren't in any particular order after the first one, which is the most important one of all.
1: Use something other than Internet Explorer. This single program is responsible for the majority of all spyware infestations. I use Mozilla Firefox instead. It's not perfect, but it's risk of spyware is presently zero, and some of the extensions for it are damn handy.
2: Don't use P2P programs. Kazaa, Morpheous, and virtually all the others come bundled with spyware, and probably the majority of the content on the network is laden with spyware.
3: Don't use pirated programs. You never know what someone might have decided to bundle along with the program when they altered it to bypass any security. Odds are, there's a good enough freeware program out there for almost every task.
4: Keep on top of Windows updates. This is one case where it's acceptable to use Internet Explorer. To me, it's the only use I have for IE. The rest of the time I only use Firefox. If I come across a site that doesn't work with Firefox, I just move on, but I can't come up with a single example of that happening off the top of my head.
Item 4 is about the only one that requires any repeated effort on your part. Microsoft tends to release new patches every second tuesday of the month, so just be sure to check the Windows Update site on, or slightly after, that day and you should be good.
Do this, and your chance of getting hit with any kind of spyware, worse than a tracking cookie, drops to near zero. It leaves you free to worry more about social engineering based "attacks" such as phishing. You won't need 2-3 programs to try and clean up the mess left in Internet Explorer's wake. You've got plenty of other things to worry about I'm sure, so why not eliminate spyware as one of them if you're able?