I've owned both. The EX500, with almost double the power, is obviously faster. Depending on the sort of riding you do, it may be more appropriate, as its greater mass and power make riding it at highway speed less dramatic.
I actually prefer the 250. They are, in reality, mostly the same, but for some reason, I always felt that the 500 felt extremely agricultural.
If you're asking "What should I trade up to from the Ninja 250?," the real answer is save a few more pennies and get a Ninja 650, SV650 or FZ07.
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