Only thing to be concerned about is if you have to cancel.
About two years ago, we went to visit my brother. We had booked two nights in a city we planned on visiting on the way back. We decided to stay and extra day a my brother's instead. Basically, had to pay for that night anyways (e.g. the "cancel before 6 pm the day of arrival" wasn't in play.)
On the other hand...sometimes if you're booking an airline/hotel and/or car deal, you can get discounts that are worth it (unless you have to cancel the trip last minute.)
So...just know what you're getting into. I've used onlines quite a bit (expedia, travelocity, orbitz, car rental companies, other) for some of my travel. Others I go through the source (e.g. Best Western, Mariott, Choice Hotel and even airlines or car rental.)