I run both Spybot and the subscription version of LavaSoft's AdAware, along with a couple anti-virus utilities, software firewalls, and a hardware firewall built into my router. Sometimes one will catch something the others missed. Ya gotta keep 'em all right up to date, of course; check for updates at least once a week, or configure them to do it themselves at least that frequently, if they will. My preference is for daily update checks.
Of course, machine resources are a consideration. All my machines have plenty of RAM memory (all they'll take) and fast processors. A bunch of stuff running in the background will noticeably slow a RAM-poor machine, and/or place a big load on a slower processor. At the very least, you should have 256MB of RAM, and a processor running at 600 MHz or better to take advantage of today's software, peripherals, and advanced webite technologies. Win 9x operating systems don't know what to do with more than 384MB of RAM, so there's no point adding more than that to Win 95/98/ME machines, but Win NT/2K/XP, Linux, and Apple OS7 and up will utilize all the memory you have slots for. Memory is dirt cheap today (unless you use RAMBUS, damnit
), and easy to install. Get all you can ... its the cheapest, easiest, most effective upgrade you can give your machine.