The keys near the rest position of the hand are 4, 5, and 6. The zero key is not in a particularly convenient spot for the thumb (it should be moved down and to the left), and the 1, 2, and 3 keys require relocating the index/middle/ring fingers from their home positions. The delete, space, comma, period, tab, equals, parentheses, and various operator symbol keys are mostly also inconveniently located, though the enter and plus keys are fine.

I don’t think the standard calculator numpad layout is defensible on digit or symbol frequency grounds.

Even if we want to keep the numbers in the standard place for the sake of familiarity, I would recommend adding some keys and relocating others, something like http://i.imgur.com/BnYqKLW.png