Don't worry about the comments bloating your CSS, you should compress your CSS before serving it on live sites anyway which will remove those.
Now if you find yourself needing to update the images inside the sprite, the process can be:
Update individual images.
Comment out Sprited CSS background images and uncomment regular background images
Remake sprite with SpriteMe, replace
Swap comments again
One of the complaints of working with sprites is that it makes updating images harder. I think this process makes it much easier. I guess an even easier process would be to have a PSD of your sprite so you can update that directly without touching CSS. If you can pull that off, great. I personally feel more organized having individual graphics. SpriteMe also gives you CSS with the locations of all the sprites, so if you needed to change the size of images or add/delete them, you'll get those new numbers automatically.
If you have your own workflow for working with sprites, please share!
Related:Setting up sprites diagonally is rather clever. The idea is then you can use the sprite as a background image of a larger box without fear of other graphics in the sprite showing up. This is at the cost of a larger sprite file size because of the extra white space.