TuneUP Utilities is a very fun toy. I'm using the trial version right now, but I'm not going to pay for it. I've been using RegSeeker for a little longer than TuneUp Utilities, and I am going to keep it.
The only thing, is that with RegSeeker you really need to know what you're doing because it will remove a lot of stuff that it shouldn't. I've spent some time adding my own things to the exclusion list, and a friend gave me a list of exclusions to add as well. I do not think that using 3 reg cleaners is necessary. One, maybe 2. Registry cleaning may speed up your computer a little, but cleaning the crap off of your PC is what really keeps it optimized.
I use CCleaner daily, and RegSeeker about once a week.
CCleaner + RegSeeker