Regardless of appraising any simulator tool, you should be aware that even "the best one" can be useless if the code were not programmed with the best practices and/or taking proper care on the timmings to interact with it; at least for me, it worked pretty well even dealing with complex tasks, as for example using a filesystem library.
Another point to remark is that not all relatives manufacturer's microcontroller variants are available on ISIS Proteus, and there are circumstances where it is even preferred to change the core on the project just to have the simulation feature on the design.