@DonkeyBets:
They're not calling with a hand, they're calling with a range of hands. You're betting against the range, not their specific holding this time.

No single hand can be considered +/- EV when Villain calls. They call with a range against which your bet was +/- EV.

"If he calls with 2-pair, that's -EV"
Nah. Not unless his entire range was 2-pair, which it can't be.
Otherwise, you get the equity from all his folds in the + column to add to the - of the times you're called and lose.
(And you have a lot of outs to retake the lead, even if you're behind when he calls.)

You get EV from their folding range and their calling range that you beat, and you lose EV from their calling range that beats you.
There are 3 terms in there.
It's the sum of the 3 terms that tells you if your line was +/- EV.

***
Look at it this way:
If you bet and they fold 95% of the time, then the 5% of the time they call (with the nuts), you're not -EV on the line. You made so, so much money off their folds that you don't even care about the 5% when they call and you lose.
It doesn't make you line -EV because they had that hand this time. 95% of the time they're just folding good equity against you.

This is what I mean when I say you're not playing against their hand, you're playing against their range.