Anyone replaced only one half of a crankcase set, any known negatives that makes this a no go.

I know a guy who had an NC21 break a chain and damage the bottom end, he replaced it with the bottom from a motor that had knackered bores.

Both the 21 and 30/35 use the NC13E engine so cases arn't too different.

They are machined as a set but the Honda quality is quite consistent.

Most people will probably say it shouldn't be done, I guess you'd need to try it and see if it fits close enough not to leak, everything line up ok.

No option of replacing both, or repairing the problem?

Considering a big bore version and do not want to disturb/experiment with the current running engine. If the idea does not work then no harm done.

I tried doing this with a KR1S and both the halves didn't line up (you could see daylight through the gaps).
They tend to be a matched set, but if they're not, then it may be possible to machine them to match up, but it's probably a whole lotta trouble