Probably not so much in aircraft (although oil collection in the cylinders would likely be as much a problem in inverted V-12s as in radials), but it would be a noticeable pain in ground vehicle and marine installations. On the other hand, conversion for right-side up upright use would probably be fairly straightforward, albeit not trivial.
There was an inverted version of the Liberty V-12 and Ranger V-770s were flipped upside-down, from their normal inverted configuration, by hot-rodders in the 1940s and 1950s.
The MB507 diesel was based on a DB603 made upright. The MB517 was however also DB603 based inverted but with a supercharger. Apparently you can get at the pistons and cams just fine.