there are many programs which are not malware, but so poorly coded, if you mistakly had run them on your system, you will regrret later.
hower manually sandboxing allows you to evaluate to larger degrre , with many restrictions apart from LUA.
for example using/working in LUA does not mean programs will be prevented to write to crtical registry settings pertaing to your user profile, i.e programs will be able to write to user hive.
if such mishaps happens and you forgotten to create system restore points then only solution is to create/add new user account in your computyter and then painfully transfer all your data.
however if you use comodo sandbox you will find all files/registry entries( wheter protected or not are written in virtual root).
A great time saver. though impact on system resources is quite high.