If you want major changes then the question becomes: such as?
There's not really much room for major changes in the way chatting is done - somewhere to type text, somewhere to view text, a list of the people on the channel - it's pretty basic stuff that can only be done in so many ways. As for mIRC scripting itself any fundamental changes are pretty much gonna wipe out backwards compatability for scripts, with the exception perhaps of consecutive space support (which I certainly would like to see). Not to mention that any big changes in the language would almost certainly be to move it towards being much more complex. Quite frankly that would be a bad thing in my eyes, the very reason I still script in mIRC is it's simplicity.
It's not like there haven't been any big steps in recent versions either, multiserver support was the one significant feature that other clients had over mIRC and when that was added it cemented mIRC as the best IRC client available.
So the question remains, what kind of big changes?