Sometimes I’ll have an instrument selected in my instrument panel and I want to change it. I replace instrument OLD with instrument NEW. The problem is Renoise plays boths instruments on top of each other. What’s the proper way to replace so OLD is completely gone.
This behavior continues even if I hit delete instrument, refill the empty spot, and hit keys on my keyboard to listen. It still has the old instrument mixed with the new.
I suppose that your problem is:
If you load renoise instrument and then load vsti (or other way) you are stacking instruments (you can use some sample for adding attack to vsti instrument for example)…
So you have to delete samples / or vsti instrument if you wanna leave just one.
But the best way for me is this, you can undo anytime you want:
This happens only, when you combine renoise instruments with vsti. And this is a neat feature, which i’m using sometimes 
Just clear the instrument, before you load a new one, when a vsti is loaded in this slot and you want to load a renoise instrument.
No change of the instrument number is needed.
If this happens with renoise instruments, then it could be a bug. Maybe you can upload a test song for bug hunting?