Most important when securing a Windows system

By far the most important things to do when securing a Microsoft Windows system is to

No 1, make sure you have the latest security related patches installed
No 2, make sure you have strong passwords on all your password protectes services.
No 3, make sure you take down all unecessary running services, uninstall if possible
No 4, have a local firewall running on your system, don't be satisfied with a $99 dollars hardware router/firewall for protection. And if you have the skills, apply outgoing packet filters to, not just the inbound traffic.

Many home users have one or more computers behind their own firewalled ADSL, Fiber or whatever they might be using. To ensure that even more security, the systems that sits on your local area network (LAN) you might have to have access rules between your systems. For example, if one of your machines gets infected and tries to spread malicious code, your other systems might survive if there is not any trust between these systems. Like firewall rules, different subnets, access lists in the switch etc.

In the end, it is always up to us, the users and administrators of the system to do our best to protect our data. The computer only performs the task we have programmed them for.