My favorite of the incredibly popular tower defense genre is the Protector series, which is now up to five titles; Protector 1 Protector 2 Protector 3 Protector 4 Protector 4.5
I'm a sucker for the Submachine series, kind of a point-and-click mystery game where no one tells you what the mystery is. Another one is the Grow series, a flash toy where you interact with some object (e.g. a cannon) by clicking on buttons corresponding to tools that do generally adorable things. If you click the buttons in a certain order, you get the best ending and you win.