Your question is the most classical, mother-of-all security questions. It is the most commonly asked question but the most commonly unanswered one because its really hard to comment.
Anti-virus
I recommend Avira PersonalEdition Classic (www.free-av.com) because it is free and has a very good detection. BUT BUT BUT if you’re having problems using it OR you just don’t like it, OR your PC is already infested with so hardto remove viruses, I suggest installing Avast Home edition because it can clean your PC using its boot time scan better than any other malware solutions out there as far as cleaning an infested (memory resident malwares) PC is concern.
Avast! is a good antivirus. It has other functionalities that you can only find in paid antimalwares. Web Sheild and Mail scanning are one of them. Although detection rates of Avast! is not as good as Avira, for a normal antimalware, Avast! is over qualified to protect you.
DO NOT use McAfee and Trend-Micro because 1) theyre not free 2) Detection rates are not so good 3) they tend to bloat your pc at the same time it is resource intensive.
AVG is improving but please don’t use it. Avast is still here…
Eset NOD32 is fast and good according to the famous www.av-comparatives.org. If you have money, then you can try it. BUT Kaspersky is also very good so if you have money, Kaspersky is a good deal.
Norton is a very good antivirus BUT it is not free, slows PC, bloats PC just like McAfee. Dont use it.
Anti-spyware
I recommend Spyware Doctor because it doesn’t only detects the malicious softwares but also cleans the files that it created. It is also free, just go to Google Packs. Spyware Doctor has the reputation of one of the fastest anti-spyware scanner around. Easy to use, very intuitive, you’ll love it.
Another anti-spyware I recommend is Spybot Search and Destroy. It is free and it is one of the most downloaded anti-spyware, and one of the first anti-spyware softwares around. One good feature is the Immunize function where in it will configure your Web browsers to be immune to malicious ActiveX downloads and installers. It can also block websites using the hosts file configurations. It can also solve some registry problems like “Missing/Disabled Taskbar” created by some malwares or the “Disabled Firewall” also by some malwares messing your computer.
So you can install two anti-spyware - Spyware Doctor as your primary, Spybot S&D as your secondary. Scan your PC once a week or fortnightly.
DONT USE AVG Anti-spyware because it is proven not helpful. It is also slow in scanning.
Ad-aware is one of the first anti-spyware. I recommend you to consider this as the last option.
Firewall
You forgot to ask this. It is important to install a firewall.
Try Comodo because it is good and free.
I hope my suggestions did help. They may not be the best but for my PC it helped me protect for the longest time.
Recap:
Antivirus (Just choose one): Avira PE Classic (www.free-av.com) OR Avast! Home Editon OR Kaspersky
Anti-spyware: Spyware Doctor and/or Spybot S&D
Firewall: Comodo