Paul Preece's Desktop Tower Defense is an insanely addictive Flash game that inspired tons of clones (which is kind of funny, since DTD itself was a "remake" of StarCraft's Turret Defense).
Here's one funny clone: Bloons Tower Defense, the perfect combo of Bloons and DTD where you get to pop baloons along a maze. http://www.ninjakiwi.com/templates/gameajax.php?name=Bloons%20Tower%20Defense%203&game=http://www.ninjakiwi.com/images/stories/Games/bloonstd3.swf - via Waxy
Previously on Neatorama: Desktop Tower Defense and Desktop Tower Defense Strategies