|Like Chuck2 said above, boot into safe-mode to run your virus/spyware scans. You are using anti-virus/anti-spyware programs, I hope (it's surprising how many people don't use basic protection). Nowadays, one program often covers both virus and spyware scanning/removal, but you may have two separate programs. Before you boot to safe-mode, update the virus/spyware definitions for your software.|
As maxsun08 stated, you can go to msconfig and uncheck anything that isn't needed at bootup. The only things I'd leave checked are anti-virus/anti-spyware, and firewall (if you use a software firewall). One of my pet hates is the tendency some software developers have to place things in startup (Adobe, for one). Note: if you're behind a proper router, it acts as a hardware firewall and a software one isn't really needed (which frees up resources).
You can also go to Black Vipers website for a table of services that can be disabled. There are a few that are enabled by default, but not needed by the average PC user. These services can use a significant amount of your machines resources. For the average user, following the "safe" column (on Black Vipers site) is recommended. You may find some services not installed, and others not on the list (BV's list). Just ignore these differences.
Defragging was also mentioned above. I'd suggest uninstalling any software that isn't needed, then defragging with a third-party defragger (the Windows defragger doesn't tidy things up like some third-party ones can). By keeping the hard drive tidy and organized (uncluttered and defragged), you'll improve the drives efficiency.
Ccleaner was also suggested above. I use it regularly to get rid of old, unneeded clutter. It also has a reliable registry utility, which can remove redundant/orphaned entries (left-over from software that's been uninstalled), increasing the efficiency of the registry. I trust it implicitly, never keeping anything it finds.
You should also make sure you have all the latest Windows Updates, but never update device drivers via Windows Update (get these from the manufacturers website).
I never have System Restore turned on, due to the ability of some viruses to infect restore points. However, unless you have an alternative system for recovering from disaster, you'd best keep it on. Before scanning for viruses/spyware, turn off System Restore, but remember to turn it back on later. You'll lose all your restore points, but it stops you getting re-infected (if a virus is hiding in there).
Download the utilities from your hard drive manufacturers website, to check the health of your drive. If it's failing, you'll need to replace it or risk losing all your files. A failing hard drive could also be the dominant reason for your slowdown problem.
Pretty much everything in my post is a part of my regular maintenance/prevention routine. About the only additional tasks I perform (apart from dust removal every few months with compressed air) are manual virus/spyware scans (just for my own piece of mind) and manual updating of Windows (I have Automatic Updates disabled). With regular maintenance/cleaning, I haven't had to contend with downtime on this machine (which runs 24/7) for a couple years. Before I realized the value of regular maintenance, I was always re-installing Windows due to slowdowns and other problems.
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