Very few web.config changes require an iisreset.

When it is required, I've tried just doing a stop/start of a given IIS
Web Site but it doesn't seem to clear all the cache. Perhaps removing
and recreating the root iis  Application?

Do some experimentation and let us know what you find.

I've not tried it, but theoretically if the Portals are using different Application Pools you should be able to stop the one in question and restart it -- without affecting the other.

I also was trying the same as ADSUTIL helps to reset(start/stop)
application pool. It works fine also. I just wanted to make a console
application to start and stop my application pool.(automation) Can
anybody help on this?

But dotnet applications, web.config file  changes does not require
IISRESET to refresh the page! but in SPS some of the msdn articles,
dotnet architects says, any changes in SPS web.config file requires
IISRESET.

Please give your comments!

Were you successful in restarting a single IIS site?

I am not sure wether this is the optimal solution. but if we stop and
start application pool where the portal  site belongs to, it does not
require entire IISRESET. but if the application pool belongs to N
number of applications means that many applications gets impact!
Right?

So, from your experimentation, stopping and starting the app pool has the same effect from a
SharePoint perspective as running iisreset. I can't imagine why that
won't work. I'll have to give that a whirl myself.

Yes. Any application using the same app pool will be affected by that app pool being reset. The real test is to just recycle the app pool and see if that does the job. Then any existing threads would be serviced by the current instance of the app pool worker process and any new threads would be started on the new worker process - providing no down time for your applications. This would be ideal - do you have time to test it for us?