I am aware of the following differences:
1) MIKESHE grid is squared as in MIKE21 classic, so, it can not be a flexible mesh as in MIKEFLOOD.
2) MIKEFLOOD do not have groundwater component as MIKE SHE
3) MIKESHE Overland Flow Component uses a Diffusive wave type of approach mean while MIKE21 in MIKE FLOOD uses a more dynamic approach.
4) MIKESHE uses a more detail approach to consider Evapotranspiration. This together with the groundwater, unsaturated, and demand-based irrigation components make it more suitable for long term simulations.
I hope this helps!