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Prototype and Scriptaculous can definitely achieve that, it's just a matter of attaching the events to the proper elements.
Have you taken a look at the Event.observe page in the prototype API [prototypejs.org]? It has decent sample code to get you started. Once you have the mouseover event block setup, just call the Scripaculous Effect from inside of it.
If you have trouble, feel free to post the code snippet you have so far and I'm sure someone will be able to help. :)