Does card size matter much?

I agree with Yamahako - I rarely see cards that aren't "standard" so I can't really comment on that. However, I do notice what a card is made from first and foremost. For example, the cards included in 'Death Angel' bug the living **** out of me, because they are so wafer-thin. I feel like I might bend one in half just by bridging a bit too exuberantly.
I have played a few games that require me to hold "not cards" in a card-like fan, and that gets me too. Strange shapes (octagons, triangles, peanuts) all irritate me to no end. My sister has a deck of playing cards that are all cut like butterflies. I can't ever figure out how to hold them.

Card size is also dependent on card layout. I've been playing around with the idea of putting flavor-art on the *bottom* of cards. I hate that unless I memorize the art to each and every card, I often have to lay down my hand in order to read certain effects and powers.
Further in that field, cards shouldn't have to be very large. Cardgames are cardgames because they are meant to represent a lot of information in several brief helpings. Nothing slows a game down more than having to read line after line of text on every card of a 7-card hand. If your cards are becoming too full with words, it's time to translate common words to recognizable symbols, and to standardize the most common rules.
There is a lot that you can do with visuals rather than words on a card. Text scares people off, takes up space, and is boring to look at. My game uses color-coded cards to denote what type they are, and effects are also color coded to match the cards to which they apply. Any math is often shown as a combination of a standard symbol, and a number. "[2]+4" (with [2] being a 2 in a red square) means that you should roll 2 red dice and add 4 to the result. If that 2 were a 3, and in a Blue square, you would roll 3 blue dice and add 4 to the result. The result is that my text is very large and easy to read, and you get a great deal of information from a simple glance. The amount of colors and symbols makes my game look very flashy and bright, and the increased space allows for bigger pieces of flavor-art on each card.

Along the same lines as above...

1) Straying from the standard sizes can increase your manufacturing costs.

2) Cards that are too small (Settlers' Development Deck) or too large (Lost Cities) can be hard to shuffle and hold.

3) Cards with non-standard *relative* dimensions (like the square cards in the Settlers card game) can be hard to shuffle.

4) The more your game depends on speed, the more you'll want to stay at or near the "normal" dimensions (at least, that's been my experience).

If you have good reason to deviate from the normal size, I wouldn't worry about it too much. At least for me, it would never be a deal breaker in whether or not to purchase or play your game. I play Settlers of Catan and Lost Cities all the time, and they both have irregular size cards.

That being said, I'd stick with normal poker or bridge playing card size unless you actually have a good reason to deviate. It'll probably be your cheapest option and as others pointed out, they're the standard size for a reason.

I'd be more concerned with making sure the quality of your cards is up to snuff. Cards that show damage after one or two plays make me sad.

Does anyone know why CCG cards are a different size (and are wider for their height) than normal playing cards?

If it's because that size is cheaper to print, you'd think that playing cards would also be made in that size.