Malware, spyware, nuisanceware-- what do you DO about it?

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As computers have gotten more sophisticated, so (it seems) have the many kinds of nuisances computer users have to deal with. Most of us are familiar with viruses and the damage they can cause to a computer system, so we run software to protect ourselves against "infections." But there's so much more out there. There's spyware-- which doesn't actually harm your computer, but may gather personal information that could lead to identity theft. There are also various forms of "grayware" that don't really DO much, except occupy space and memory on your system. This stuff isn't always an actual "invasion," sometimes it's merely a nuisance-- the most harmless and mainstream software often runs background processes that accesses remote websites to update itself on a regular basis. Some include routines that mess with your computer's settings, ostensibly in the name of "efficiency." I have one piece of (useful) software that causes a conflict that turns my speakers to "mute," every time I run it. Everytime we face "technology challenges," bunches of "technology solutions" come to market. Unfortunately, many of the so-called solutions are little better than the original problems. "Anti-spyware" programs have their own embedded algorithms that-- in effect-- "spy" on you and report back your web surfing and computer habits, all in the name of "working better" for you. So my question this morning, for everyone, but ESPECIALLY for the serious computer g33eks out there is what IS the most effective/least invasive malware/spyware detection and removal software out there? Something that doesn't just create a new set of problems, and doesn't just create it's own "spying" elements. And I don't want to have to manually edit registry files and so on. What's YOUR opinion? Have you found something that really WORKS, but without just creating a new set of problems?