Not having to copy big arrays when calling unmanaged C dlls from .Net will be great for performance. I wonder if this is going to open up new security holes though.
The use case for Span is more within the managed realm: it allows pointer-like manipulation of memory, without having to special-case it for each type.
And although anything with pointers is of course asking for trouble to some extent, you don't lose any safety in most scenarios (those not involving obvious giveaways like 'unsafe'...)