D365 is a generic term that references quite a lot, this is in the AX migration forum therefore the presumption is it is D365FO (Supply Chain and Finance apps).
1. Layers is a concept for AX2012 really, whilst they still exist they do not perform the same functionality. In essence the ISV shifts to extensions, and it is a different approach. The ISV handles this and the impact will be zero on the assumption the ISV is valid on the current D365 version.
2. ISV's are listed on the app store. Customers will use ISV's dependent upon business needs. This in part leads to point 4, you assess your system, what you need, reassess use and new functionality (and deprecated). What you purchased and how you used it may have changed, justify the value of the ISV to move forward and reinvest.
3. What are you looking to overcome whilst upgrading, as this is mainly about ISV's you would need to validate use and then validate your current ISV still exists.
4. This will be the case to many clients, as an example WHS in AX2012 saw many use the Blue Horseshoe solution, Microsoft purchased this and it is now part of the main product, the old WMDP was deprecated and therefore you would need to assess this anyway. It might be you still need the Blue Horseshoe extensions!
This is probably a specific client by client project by project question. I find that many, due to the change in business and requirements aligned to technology see the migration process as a reimplementation ore than an upgrade.