There are a number of possible solutions such as Phonegap and Appcelerator. Both of these tools are ideal for developing apps for mobile platforms such as iPhone, Android and Blackberry.
As for the actual design....
Try and make your app as native as possible on the host device. For example if you're target is the iPhone make the navigation and controls as iPhone-like as possible. If you deliver a user experience on the device that fits in well with native software and menu controls this will make your app much more user friendly.