Nothing beats native. I've tried Appcelerator and you'll get to a point near the end where you've got to do the other 80% of your application and the third party framework is going to fight you till completion, or some state of completion that you're ok with. One of the problems is that the simplification also requires you to give up your power. If you're doing a simple application then maybe a third party tool will…
PhoneGap + jqtouch (or perhaps jquery mobile as it matures) is an awesome way to get going fast but that last mile can be torture, especially if you're working with an uncompromising customer/designer/etc.
At some point someone is going to throw on the brakes because "x doesn't y like an iPhone app" and then it gets ugly.
I think that you can do some very cool stuff using the "web app in a can" approach and I think it's appropriate for a lot of the typical "corporate"-type apps as long as you can manage expectations and stress the cross-platform angle (which can be almost zero-effort, check out https://build.phonegap.com/faq).
But pistoriusp is right, if you're breaking new ground then time invested in learning the native way is well spent.