A good article to address this :http://www.tomshardware.com/faq/id-2386844/computer-slow.html
In short, The biggest problem I experience is over time when you install/uninstall software there are many "orphaned" files that are left over. I like to use IObit Uninstaller that will search for and remove these fragments that are left over. Like someone posted earlier, programs when they get installed, write information to a database called your "registry". These entries build over time and it takes longer for your computer to scan over all of the entries when it boots.
Second, another bang-for-your-buck item is explained in the article I linked to and that is "startup programs". There are many popular programs that install a startup application on your system meaning everytime your computer run, these programs run in the "background" using up your system memory resources. Among them are iTunes, Adobe products, and many others. Removing many of these programs from your startup will increase your speed and other than anti-virus or backup programs, many of them are not needed and only provide "update capability", however, when you run the program it will check for updates anyway in most cases.