I win most Defense games by two factors: High Income and Spam. I simply use the tactics of a War of Attrition. If you have money and numbers, you win. This goes for about any game whatsoever.
The first thing you should upgrade when playing defense games is your income, as this simply allows you to buy everything else you need. Granted, some games try to eliminate this trait, making it where you cannot simply be a defenseless cash cow and will need to get something to keep you alive early on, usually costing not a mammoth amount of cash, but a sizable one.
Much like a swarm of bees attacking a black bear, the swarm will eventually win as their numbers overwhelm size and power. However, be wary as there is a power vs numbers factor, or as I call the "Spartan" variable.
If you can calculate the amount of spam needed to win, you can overwhelm an opponent, regardless of their power. [Again, note the Persians vs Spartans in the Battle of Thermopylae.]
