I do it myself (I like things arranged neatly!) without any major problems. However, I have heard it upsets Software Update I don't use it myself so I can't advise on that. The only problem I had was with the Dictionary App. The 'click-on-a-word-and-it-gives-you-a-definition' feature doesn't work if you put it in a sub-folder it needs to be in the actual Apps folder.
To solve the problem, I just moved it back. You could have a try with the sub-folders and if you have any difficulties with an app, move it back.