The biggest change made in Alfresco Share was between versions 4.1 and 4.2 when all of the WebScripts were refactored to move all the logic out of the FreeMarker templates and into the JavaScript controller (see the series of blog posts starting here). The purpose of this was to make customization easier as it enabled simple configuration tweaks as well as swapping out default Alfresco widgets for 3rd party extensions. This somewhat paved the way for the approach that Aikau then follows - namely to allow all customizations to be done through the WebScript JS controller but with Aikau the widgets are much finer grained.
Ultimately it is going to entirely depend on your customizations for 4.1. The main differences you'll find are to the header bar and to the search page. The toolbar and documentlist Surf Components were also merged to reduce the vertical space that they took up.
The main issue for other WebScript customizations will be that you'll need change how you were extending them, as code that was previously in the FreeMarker template in 4.1 will now be in the JS controller.
