I found my 3DS (original) ridiculously uncomfortable to hold. I had to buy a grip for it; while it's an improvement, the Vita is much more comfortable to hold, outside of annoyances like the back touch pad and the sensitive touch screen that's also close to the d-pad.
I honestly don't like holding the Vita much. The rear touch panel is a problem. Also, the tiny face buttons don't help. I bought the trigger grips and it fares a little better though I wish it wasn't rubberized plastic.
As for the 3DS (regular) It's a bit easier for me to hold, but after playing for about an hour the glossy finish becomes sticky and makes me feel very uncomfortable and then there are the sharp corners. I have virtually no issues with the 3DS XL though.