Here are a bunch of ways to make it unique:
-Make your own terrain, and make it hilly. I've never seen a hilly TD. You can also add all sorts of tweaks to the terrain, such as in some regions the creeps are invisible, in others, they move at double the speed, etc.
-Think of a unique way to make the towers. Such as - the towers slowly grow larger as time passes, or something else. (I'm making a TD myself, so it's a little hard for me to come up with unique things that I haven't done yet

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-Give really wierd abilities to the towers.. think towers that randomly disappear and reappear somewhere else, or towers that slowly move across the map.
-All towers are built on a railroad car, and instead of the creeps moving towards you, you move towards the creeps. The car takes a weaving path through the creeps and then comes out the other side, and when it comes out, the creeps all run forward to the end. The railroad car would be really long so that the players could build in a string.
-The creeps are on a big conveyor belt that slides them from the start to the end. Since they're not running, they can take the initiative and group together in the places where they are least likely to be hit, making it slightly harder to hit them
-I'd suggest something about towers that increase the stats of other towers, but I'm already doing that so it's not unique
-The creeps spawn randomly throughout the map, and you have to kill them before they reach the center.
-Creeps self-destruct when they die, dealing damage to any towers near them.
-Creeps can go underground (when creeps run into a region they move instantly to a point off the map, some time goes by, and they move back onto the map somewhere else.
-Take some ideas from the TD Wars thread that aren't being used
That's as far as I can go for now, post later if you want some more
