A genre is an expectation. Pick up a game that labels itself as a first person shooter, and there are certain things that you'd expect to see. These expectations extend beyond the obvious and into more intangible properties, like pacing and story. For example, a game which is labeled a first person shooter is expected to have a fast, tense pace with buckets of action. These expectations are usually adhered to, and perhaps no genre is more conservative in this regard than the tower defense genre.
But appearances can be deceiving. The same things might be said about the platforming genre, and yet Braid demolished expectations for what a platformer might be by introducing brilliant writing and unique gameplay mechanics. As it turns out, the tower defense genre has also had its Braid. The name of the game is Immortal Defense, and it completely upsets the expectations of a the tower defense genre.
A normal tower defense game might not even have need for this section. A normal tower defense game would include a couple paragraphs about how hoards of X are assaulting your Y with unimaginable ferocity. They must be stopped, of course, or else horrible consequence Z will occur. But Immortal Defense goes the extra mile and introduces one of the most interesting and literary stories that I've seen in any game.
You are a Path Defender. The government of your planet, called Dukis, made you a Path Defender in order to fight an enemy known as the Bavakh. As a Path Defender, you exist in Path Space, a level of reality beyond all others. To you, the routes which starships travel to get from one point to another show up as nothing but simple paths, and as a result you're perfectly suited to defend your planet. This is done not with structures, but with manifestations of your psyche known as points. These points have their own personalities, and they express themselves in the game through simple text messages that appear on the screen. Upgrade a point and it might thank you. Place it well, and it will occasionally celebrate the number of kills it has been able to achieve.
This all sounds very detached from reality, but the game also makes it clear that although you are a Path Defender, you were once a mortal person. In order to defend your planet, you left behind your wife, your unborn child, your friends, and likely the chance to ever return to mortality. This is a point the game does not take lightly. The game's story is held together by paragraphs of text which appear at the beginning of each level, and these are often messages received from your daughter and, eventually, your grand-daughter. The story of Dr. Manhattan from The Watchmen seems to be a heavy influence on this game, but I dare say that the story of Immortal Defense goes even further in its exploration of the consequences of immortality.