Running the World of Mists
The first problem when running any Spelljammer campaign (not just Mists of the Void) is the lack of much reference material. While anyone doing a groundling campaign (or even Planescape) can draw on vast numbers of books, several movies and a general feel for the subject matter potrayed. The basic idea of a high medieval (or early rainissance) society with added magic seems to be relatively easy to conjure. Spelljammer is also based on this, but it is for more fantastic.
Attracting Players
The first problem is attracting players to the idea. While sailing the void on an animal-like sailing vessel may be fantastic for the characters, they are not really going to question it. After all it is happening to them in a world were meagic is real, allowing people to throw fire, ice, acid and more at enemies, heal wounds in an instant, change shape, where dragons and weirder creatures are real, a flying ship, even one capable of leaving the world behind will be unusual, but not beyond conception.
On the other hand the players of those characters live in the real world with a rather harsh science, where magic is only imagination and being tossed into the void unprotected means decompression and a quick and messy death. Something the size of ship cannot produce sufficient gravity to create an atmospheric envelope, so that all space vehicles are actually enclosed. Technology seems like magic to many, but it is in the end far more messy and dirty.
If players definitely do not want to go into spelljamming, because they just considere it to weird, there is probably no way to get them in the boat, but I don't think that the idea is any more strange than the reality of magic and monsters. The original setting just changed the laws of physics to accomodate the setting, which is a valid path to go, because the physics of a universe, where magic is an undeniable reality are probaby different from thos of the real world. I prefer an approach, where the change is less invasive, and the ships rely even more heavily on magic.
The ship's 1G gravity and atmospheric envelope are created by a magical item, which is literally its backbone (and ribcage), the spelljamming backbone, Actually this item does not create point-based gravity, but planar gravity, its plane usually near the bottom of the ship. This item is, of course, in addition to the spelljamming helm, which provides the actual motive force by draining the magical energy from a spellcaster or psion.
One last consideration is the necissity of travelling that way, when the use of gates and plane shifting magic is a lot faster. These are pretty high-level spells, which are only available to high-level characters, which also makes them expensive to be cast by an NPC mystic. Hiring as (fighting) crew on a sailing or spelljamming ship on the other hand is likely to be relatively low cost, or may even earn the party money. Besides people still sail and travel with caravans along trade roads instead of using magical transport and most of the spells are not very accurate.
The Atmosphere
The second challenge is getting the feeling right.
Reading List
Unfortunately the reading list for spelljammer is very short.