I've been trying to get a better understanding of game theory, and it's causing me some confusion in some spots. I understand that as a general rule, we have to be defending on each street at a frequency that prevents our opponent from bluffing the worst 2 cards in his range. So when faced with a pot sized bet on the turn, we should defend roughly 50%. But if we to look at the situation in a vacuum with our specific hand, give him a range, and try to estimate our equity VS that range, how applicable is that % given that there is another street to play?

For example suppose we think we have 40% VS his range on the turn and are getting 2-1, so if we knew no more bets would go in it would be a call. But he has also now bet flop and turn, and it looks like he should be able to bet the river again with something resembling a polarized range. Am I correct in my thinking that his bluffs, if he is balanced, are also "wins" for him since both calling and folding with give me an EV of 0? So on the turn we have to account for that, and our equity is a little deceiving? Thanks for any help.

This last bit isn't correct.

If there are streets left to play, then you can't make a call-or-fold decision based on pure pot odds (i.e. equity) considerations. You have to take into account the possibility of future action -- implied odds, reverse implied odds, hand playability, etc. Calling might allow us to capture more of the pot than our equity suggests (e.g. if we have a draw and good implied odds) or worse than our equity suggests (e.g. if we have a made hand that figures to act like a bluff-catcher if we face future bets).