There are some cross-browser issues you will have to watch out for, but you'll find them with experience and figure out how to get around them.
Well isn't that what JQuery, Mootools, and other JS libraries are for?
I haven't used Mootools that much, but I have used JQuery a fair bit. I like the design of the interface a lot. Unfortunately, I think it adds a lot of overhead, especially on mobile devices. I don't think there are *that* many cross-browser issues to warrant such a huge cost in download size and startup time. Yes, the issues are annoying, but they are really easy to get around, and then you've learned it and never have to deal with it again.