For me personally, I would pick the Betty over the Denim Spy for the following reasons.
1. I think the Betty's style isn't one to ever be out. Someone will always be toting around a bag like that, it's highly functional. The squirrelly spy, though very cute, will date a lot quicker.
2. Your wardrobe. Betty is subtle enough that you could probably take it out every day and people wouldn't notice the bag screaming out to them. The Squirrely Spy is much louder (though very cute), but I think if you carried it for a week straight, it'd seem tried whereas the Betty wouldn't.
3. Betty costs a whole lot less than the squirrelly spy and it's leather. For the price of the Denim Spy, you could buy the Betty and another bag.
CONS: That Denim Spy is awfully cute and more fun. For me, I'm not sure that the Denim Spy would have the longevity that the Betty probably would.