we recently started onboarding nvidia GRID VCA as a solution for our customers in your situation: http://www.hawkridgesys.com/products/nvidia/
i think it is the best solution as long as you have a good network connection. we had some challenges implementing it internally because our VPN was slow but we switched from an SSL VPN to an IPSEC VPN and solved that problem. your users' experience would be the same regardless of whether they were at work or at home and you'd gain all the performance and productivity benefits because the GRID is directly connected to the files.
the only thing this doesn't address is mobile users that need to be completely offline (like on a plane). for this, i'd go with enterprise PDM. pull down local copies of the files..etc so that it is like what they have at work. and for user settings, my experience is that users just "deal" with having 2 sets of settings. that being said, you'll want some file locations set so a small .reg file with those to point those locations to the right place in the vault is probably a good step to have.
feel free to contact me at firstname.lastname@example.org and I can connect you to the right person to talk to about those solutions.