It's all pretty much a binary search of trying to divide the candidates in half with half lower and half higher. I occasionally tweak that when I think certain candidates are more or less likely or that if I use a certain guess I will prompt a (yyy - X) is a square number or (yyy - X) is prime clue. That's the same logic of why we start around 500.
Again, it's important that it's dividing the candidates in two and not the remaining numbers. I describe that above when I discuss what I do with "x > 499; (x-499) is a perfect square," Guessing 755 (i.e., 499 + 16²) would be the closest to the midpoint of 499 and 999. The remaining candidates are 499 + 1² through 499 + 22². That suggests using 11². However, because I think 4², 8², 9², 16², and possibly 1² would all have generated different clues (e.g., "(x - 499) is a perfect 6th power" for 563 = 499 + 8²), I think 13² is probably best as it divides the remaining choices in evenly...8 above and 8 lower.
13² has a secret bonus of possibly triggering "x < 668; (668 - x) is a perfect square" if the solution were 524 or 643, thanks to the Pythagorean theorem and the 5-12-13 triangle. Now that I think of it, 12² is even better for this since you'd have a 5-12-13, 9-12-15, and 12-16-20 triangles all as options. "x > 643; (x -643) is a perfect square" for 668 or 724 and "x > 643; (x -643) is a perfect 8th power" for 899.
While I (obviously) tend to overthink things, this was the first time I noticed those 12² options. I rarely anticipate the "(x + yyy) is a perfect square" type clues, though I love it when I get them.
Similarly, I don't necessarily go through listing out all the candidates after the first clue, especially if I start with a mediocre-to-bad clue like "x > 499; (x-499)'s largest prime divisor is 5." In that case, I'll just guess where the midpoint among candidates will be, use something like 679 (= 499 + 2² * 3² * 5) and hope to get a different clue next. I wouldn't be surprised if 659 or even 619 were better, here, but I can't be bothered.
I hope that makes sense as to what my thought process is on subsequent guesses and what kinds of things one could consider if you wanted to play optimally. I do try to strike a balance in how much time to spend to try playing optimally vs. getting the thing done more quickly.