I work in an environment where previous developers roped the company into using both JQuery and Prototype...and it's a mess. Not only do we have to work out of compatibility mode, but just think of the extra overhead that it causes. When debugging, Prototype "hijacks" debug messages in Firebug, which leads to even more work. And the maddening part is that I've been undoing this mess for months and am just starting to get close to being done with it....and just when I'm about to pull the plug on Prototype I always seem to find another section that relies on it...
It's for this reason that I argue every time against combinations of frameworks that have similar purposes. For example, no matter how cool you might think YUI Grids is, if you load the entire YUI Framework you best not be doing Jquery, Moo, or Prototype. You'd be just needlessly bogging yourself down. It kills the load time (which wrecks the user experience) and just gives developers headaches and needless work.
Look at this phase of your site like building the foundation. You have the opportunity to use anything you want to use, but you have to be careful not to "paint yourself into a corner" so to speak. So, use purpose-built and best in class tools that are available based on your resources. Don't just use something to be cute! We're lucky in that many very high quality tools are free, so we have a choice. But know that you're steering the direction of your site for the future, and you might be the person like me who has to deal with the consequences if your decisions are hastily made.
So, unless you're NEVER going to use another framework, I endorse Reset...or even just doing top quality standards compliant CSS.