If you have to deal with really large data sets in GRASS GIS, you might want to check out the new GRASS Wiki category; Massive data analysis. It contains a lot of good information and suggestions what you can do in such situations. Markus, who shared this link in a comment on an earlier post, also suggested to use GRASS 7, which is being made large file support (LFS) compliant. I am using GRASS 7.0 for some time now, and I would add to that version 7 has a much improved vector handling, and numerous other improvements and new features.
If you decide to give it a try, be aware that the GRASS 7 vector topology format changed in GRASS 7.0, and is not fully backward compatible. This means that if you want to open a vector layer created in GRASS 7.0 in GRASS 6.4, you need to rebuild the topology first . This is not a big deal really. After opening the layer, right click on it and in the context menu, select ‘rebuild topology’. Do the same when opening GRASS 6.4 vector layers in GRASS 7.0.
There is even an option to rebuild the topology of all vector layers in a mapset. Go to the vector menu and select ‘Topology maintenance | rebuild topology on all vector maps’. Or use the v.build.all command on the command line.
You can, and I would recommend, to keep both versions for the time being. Although easy if you build from source, I am not sure how that works when installing from a package or on Windows. But there is always Google, I am sure the answer is out there somewhere.