Baloons Tower Defence is one of the best know games in this area. And the 4th sequel to the game pushes the limits of perfection. Ballons Tower Defence 4 or BTD4 has better graphics, lots of new and interesting tower types and tons of upgrades. In this game you can save your games and play for hours in the career mode. But you should also try the sandbox and apocalypse modes.
You only need to select and track and difficulty then you are ready to go. Use the side bar to purchase new towers and upgrades, place them on the best spots for maximum effect.