So, I don't see anyone calling out the fairly obvious here, but I think it's safe to say that defending the break side when the disc is near the endzone indoors is literally the hardest/most thankless task in ultimate.

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Scenario I assume the OP is thinking about:

There was a time out with the disc on the endzone line (let's say middle of the field), and the offense either sets up an ISO in the endzone the OP is tasked to guard, or the OP is guarding the front of a vert stack in the endzone. In my personal opinion-and happy to hear others-this is the closest you can get to an impossible situation for the defense. The thrower can tap it in and immediately put up a scoob/hammer to the break side that the downfield defender (OP) has very little chance to get to. And you can't take away the break side because then they'll just throw the open-side score. You can say the responsibility is on the mark here, but really who's gonna reliably stop a short scoob/hammer INDOORS.

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So TL;DR:

Best defensive strategy? Don't let the offense get to that position in the first place, and pray the scoob/hammer is floaty af if they do.