Seriously though, there's isn't any anti-virus software that can detect everything. Malware coder's can possibly make something that shows up clean and undetected on
https://www.virustotal.com/ or
http://virusscan.jotti.org/. The difference between most antivirus software is their speed on updating their software to detect the newer malware. I would think half that effort relies on already infected users to upload samples for them to analyze.
It's not a bad idea to keep multiple scanners handy like malwarebytes, spybot and MSE. MSE/Windows defender isn't the best but its free. You can install it and disable the the real-time protection too free up cpu resources and just use it as an on-demand scanner and optionally use an alternative paid/free antivirus software on top of that. Some say Combofix but I wouldn't just use that casually. You'll need to know exactly what you're doing with it because it can potentially kill your OS. Combofix is usually used as a last resort. In those cases, it's best to just do a fresh install of windows or better yet, restore a cloned system image of an already configured OS install made with Acronis, Paragon, Macrium, DriveImageXML, Clonezilla, etc. or the built-in Windows backup.
Common sense is the best anti-virus. As a power user, I don't even have a realtime/background antivirus scanner and have UAC disabled. I occasionally scan with malwarebytes, spybot and MSE. If I need to use something shady, I run it through a sandbox via VM or sandboxie. Don't just blindly open every executable out there. Browse the web with javascript disabled with the help of NoScript and only enable on trusted sites.
Meanwhile there are people I know who have UAC on by default and run Norton, nod32, avast, avg, kaspersky and other stuff that have a crap ton of mind boggling malware like trojans and keyloggers messing up their system. Where do they catch this stuff?? I mean I probably go through warez and filesharing sites more than casuals do but I never get any OS crippling malware. I bet most of the malware comes from social engineering crap like phishing, fake websites selling antivirus software, scam emails and the like. Only idiots fall for that.
Most people use scanning speed and cpu/ram usage as a basis to compare everytime a "What's the best antivirus?" thread is made. Pointless if you ask me. What websites do they go to and what software do they use that somehow has malware in it? You know, so their preferred program gets some testing. It's always "oh i've been using kaspersky for years and my pc's been clean" or "Avast is great and uses few resources". If you haven't caught anything then how would you know if one antivirus software is better than the other? The only way to know is to read benchmarks online that test already known samples of malware and see if the various companies have their scan engines updated to detect them. Even then, rankings constantly change meaning there isn't one reliable software to use.
TL;DR: There's no reason not to use MSE because its free and is perfectly fine to run alongside third party scanners and there's no excuse to rely on it alone. Safe browsing habits, MSE + third party scanners is best way to go. You need trigger discipline to not accidentally shoot yourself. You'll want a riot shield to go along with that kevlar vest and helmet because none of them are completely bulletproof. Finally, situational awareness so you don't go running into a crossfire. Not one single Antivirus software will completely protect you. Just running the top rated antivirus sofware and thinking your perfectly safe to go ham on the internet is a bad assumption to make.