I've nuked twice. Once because my town was a mess with random stuff here, there, and everywhere. I wanted something nice for my start screen. I nuked again after I got all the land for SH. I wanted to put my mansions ove there and I didn't want to keep all the SH stuff in SH and trying to shuffle everything around seemed impossible. Plus I wanted room for my forest which had been clear cut to accommodate new stuff. I've given up on my start start screen. Ever time I get my park centered, they add more land or have an event item dictate the start screen. So my start screen is whatever it is. My SF isn't perfect and I still have several areas that need work, but it looks so much better than it did. I'm going to shuffle for the time being. I've got a good start on incorporating the monorail into my town. It'll take a while to get the tracks I need, but I'll keep grinding for recyclables.
If you still have toxic waste, it won't get stored. You may want to stick some in strategic places before you nuke. Trying to navigate with no landmarks is tricky and I deffinately nuked on a Friday night when I didn't have much planned for the weekend so I could get it back in shape relatively quickly. I also did KL first so I got an idea of what I was getting myself into. Good luck!