First off, check your VST Devices setup and make sure that you have the Asio driver selected for your audiocard.
Menu Devices>device setup>VST audiosystem
Secondly, go to VST connections (usually f4) and check your i/o.
If you're only seeing mono inputs, create a new stereo input and map your mono audio card inputs to it accordingly. This way you'll have ganged stereo inputs.
Usually the audiocard has its own mixer that you can access through the control panel; Nuendo lets you access this with the Asio panel under VST Audiosystem, but not all soundcards support this and you might have to access it via a systemtray menu or however the soundcard does it.
Some soundcards have switcheable line/mic inputs on the first 2 inputs, and again updating the driver might reset these settings, causing more (or less) input gain then say on input 3 and 4.
The control room that keeps being mentioned is a feature where you can create a control room section within Nuendo, complete with talkback, seperate headphone sends and returns.
If this is on, on some occasions it can cause an increase on certain outputs if for example the main monitor and the 1st headphone outputs are routed to the same audiocard output.
Unfortunately it is a complex feature which the manual can explain infinitely better than I can
To quickly check if it is on, go to VST connections and check the tab called 'Studio'. If you don't want to use it you should disable it.
Hope that helps....also, check the manual, it's a pretty nice read!