Better late then never, I just wanted to add my experience with this in case there is still any interest.
I was in the same situation about 6 months ago. 4 x 2TB drives and down to my last 300 Gb of free space. I wasn't keen on adding an eSata tower, not least because they're pretty expensive for a decent one these days, at least here in the UK. So after reading the guides several times (the ones linked to by lioninstreet in his reply above) and backing up all my data to an external USB drive, I purchased a cheap 4TB HGST Ultrastar drive off ebay and decided to try a little experiment.
The guides are very useful and informative, hats off to the individuals who have shared them. Between them they contained most of the infomation I needed to successfully do this, but I found when attempting to follow them, the odd step was either missing or not quite correct, at least for me at any rate. After a few initial failures, some trial and error, and probably a bit of dumb luck, I managed to successfully replace one of the 2TB drives in the pool with the 4TB one. It's been nearly six months now, and everything is still working great, the 4TB drive is over 80% utilised within the storage pool and I've had no errors to date.
A few things I learnt that aren't covered or are different in the guides.
1. Before you begin, you need to make sure you have updated the Intel SATA controller driver for your MSS (iaStor.sys) to 10.1.0.1008. This was the cause of most of my initial problems in getting the MSS to correctly recognise and format the 4TB drive. You shouldn't need any third party apps to format and partition your disk once you do this, disk management works fine (at least it did for me).
2. Stop the Drive Extender Migrator service BEFORE you add the new drive to the storage pool. This will save you a world of pain later on, trust me
](./images/smilies/eusa_wall.gif "Brick Wall")
3. When you stop the Virtual Disk service, you will need to restart the Windows Home Server Storage Manager service, otherwise you will not be able to use disk management or diskpart to prepare the disk.
4. Within the mount point files that you make a copy of before you delete the MBR partition, you will find a WHS.reg file. I found using this to compare to the registry after you have edited it as per the guides helped in tracking down and fixing any remaining errors.
5. Use an AF disk that has some form of smart align/emulation support and avoid any sector alignment problems.
One last thing,
I mentioned earlier that I back up my server to an external USB drive. It's a 6TB Seagate Expansion drive, it was preformatted to NTFS out of the box, I just plugged it in and selected to use it as a server backup drive. It has always shown the correct capacity, and backups have always been succesfull, even before I updated the SATA driver. I'm curious to know how long other peoples USB drives worked for before they went RAW, was it longer than 6 months?
Hope this has been of interest to someone and I've been able to payback a tiny piece of the huge amount of help I've found in this forum over the last 10 years.