Here's a suggested list of some of the items that should be maintained
on your computer and some suggestions for added security. Basic
maintenance and basic security work together to keep your system
performance at its peak. Like your vehicle, a computer is a complex
item that needs routine maintenance and basic security to keep it
running and free from problems. Keeping a clean and maintained machine
makes for a smoother operating computer.

It may sound like a lot to do, but breaking it down and doing some
occasionally should make it simple. Plus, if you start off on the right track you'll save headaches down the road.

It's difficult to say how often these items should be completed. Your
computer is different from others and your use is different, so your
time frame may differ and that's fine. This is intended to give some
ideas of the types of things that should be done.
Add/delete/modify as needed.
The point is to establish a routine on a regular basis.

First, some of the basics:
For the most part, these items need to be done only once.
(Should be done immediately when getting a new machine)

Rename user account disable guest account & password other accounts
Install a firewall

Install an antivirus program

Install a spyware/malware remover

Install a spyware blocker

Install a trojan detector

Install a registry guard

Install a program to edit your startup programs

Uninstall preloaded programs that you won't use

Secure browser & email client settings

Setup "popup" control or install popup blocker

Customize settings for all installed programs

Check for current versions/updates on all software, including the Operating System.(OS)

Disable "Messenger" unless needed

Replace/disable programs that "phone home"

Determine how you will back up critical data

Install surge protector or UPS

Record serial #s, product key #s, model #s & specifications

Make (and test) a boot disk

Back up drivers and special install disks

Clean up the startup programs

Perform as needed:

Backup vital files on a time frame appropriate for you.
If you have a
lot of important data that is updated/added frequently you'll need to
backup more often than someone who has little critical data.

It's also a good idea to change your passwords periodically

Items needing attention regularly. Suggested time frame: Weekly to
2x/month

Update definitions on any program running in the background, such as
a real time virus detection.

Run virus check and spyware check (if not done automatically)

Clean out junk mail and old email

Clean cookies, temp files etc.

Empty recycle bin

Backup registry/set System Restore point

Suggested time frame: Monthly to Quarterly

Disk check & Defragment

Check for OS updates & patches

Suggested time frame: Once or twice a year

Clean keyboard, mouse, mouse pad, monitor, vents & case

Uninstall (don't just delete folders of) obsolete & unused
applications

Clean out old downloads and files that are no longer needed. Also
check for ~*.*, *.tmp, *.chk, *.old, file0*.* and other similar files

Clean inside case (blow out dust, check connections etc), including
power supply

Check that fans are working

Clean out excess startup programs
Clean Start Menu

Clean & organize files

Check hard drive space - should be >20% free space

Clean index.dat files

Clean out Bookmarks/Favorites

Clean out excess graphics files

And also,

Don't forget to unplug your system and phone/internet connection
during thunderstorms!

Document error messages so you can research them or ask for help

Pay attention to strange sounds and noticeable changes in performance

Thanx to (Cynic) Ken for this contribution