I posted a reply elsewhere on some similar points, but I'll go into more detail here.
What I like to ask is what project or achievement people are most proud of. That forces them to use their own subjective judgment rather than attempt to cast about for some sort of objective definition of "significant".
There are many reasons why I love this question.
First off, it puts things squarely into the realm of the real instead of the abstract. It can tell you a lot about whether or not you're dealing with someone who gets things done or just someone who "does work".
From there it's a quick jumping off point into the specific skills and competencies of the candidate, viewed through the lens of productive work. It's a way to see what skills people have in sort of a sideways way, because you see what skills they actually use, rather than the skills they tell you they have.
Perhaps most importantly, it tells you about a person's priorities and values. It tells you the sort of things they think are important. Did they do something that actually delivered value to anyone? Did they do something that required overcoming obstacles or did they just cruise along and build something "cool"? Or something that was technologically sophisticated but useless in practical terms? Do they value titles and money over real accomplishments where something of lasting importance or value is built and delivered to users?
It also gives an opportunity to explore a lot of issues that are hard to suss out otherwise. For example, does the candidate have initiative or do they just follow along? Do they strive to improve the way things work or just tolerate the status quo? That can be evidenced if the project they describe was something they took on of their own accord or was handed to them, whether it was an internal improvement project, and whether they had to fight against the establishment to get things done.
So there you go. Values, skillset, competencies, initiative, and ability to execute. You won't necessarily get all of that out of a candidate every time you ask such a question, but there's no such thing as a perfect interviewing technique.
For someone straight out of college or without much experience of course you have to modify how you interview them, but that's always going to be true, and sometimes this same question can still be valuable, just not in exactly the same way.
P.S. Also, just having a good set of questions or a good process to go through is not enough to make someone a good interviewer. Interviewing is hard, easily one of the hardest things in the profession, and only a small subset of folks who do it are actually good at it. I don't know exactly how to make a bad interviewer into a good one, that's a subject that could fill volumes and volumes. But I think this particular kind of question is, on par, much more helpful than not and a step in the right direction.