Xref's will need relative paths instead of absolute paths, among other things.

This is something where I would highly recommend some aftermarket integration.

This is also probably the only time I will suggest using folders in document
libraries.

Here are some of my blog posts about my pain with AutoCAD and SharePoint.

slingeronline.wordpress.com/.../do-you-think-autodesk-got-it-right\
-this-time-yeah-me-neither/

slingeronline.wordpress.com/.../foiled-again-dwgtrueviews-evil-way\
s/

slingeronline.wordpress.com/.../cadworx-flexcad-smartpid-and-other\
-autocad-plug-ins-with-moss/

slingeronline.wordpress.com/.../autodesk-sharepoint-and-the-useles\
sness-of-autodesk/

slingeronline.wordpress.com/.../

slingeronline.wordpress.com/.../autodesks-answer-to-true-view-does\
nt-work-either/

slingeronline.wordpress.com/.../more-on-the-sharepointdwg-true-vie\
w-front/

slingeronline.wordpress.com/.../

slingeronline.wordpress.com/.../the-continuing-saga-of-autodesk-gi\
ving-their-users-the-finger/

slingeronline.wordpress.com/.../bentleys-microstation-autodesks-au\
tocad-and-microsofts-sharepoint/

slingeronline.wordpress.com/.../dwg-true-view-and-sharepoint-dont-\play-nice/

slingeronline.wordpress.com/.../

slingeronline.wordpress.com/.../

I think my recommendation may have to be "wait until your
SharePoint solution is more mature and then we'll talk about adding AutoCAD"
-- or maybe we'll just keep those in external storage somewhere.

One of the things that we didn't try at that company was using RBS. This may be
the answer you are looking for. (I was a brand spanking new admin at this
company, and I missed a lot.)

Thanks for the initial thoughts, everyone. Another question: has anyone
here used a third-party CAD mitigator with a hosted SharePoint solution like
MS Office 365?

The issue isn't the car document themselves but the X-refs contained within
them. That is where the document break down