Many good points made in the above post, and I do often feel the process is more musical/physical, and overall more fun with hardware knobs.
Although I've found as much as I enjoy interacting directly with hardware, if I played out my ideas first without immediacy with regard to software integration, my ideas will probably get lost (or important components of originally inspired idea dropped) as I try to port that idea over to the software environment for proper recording/producing.
With regard to tweaking 2 at once, as you mentioned I think it is best done in conjunction with a midi controller. I tend to map the modwheel temporarily to one parameter, work it with left hand, and work another parameter with the mouse. There are also a number of X/Y axis solutions (Zebra and some others have this pad built into the software), or it can be done in any VST with a DAW X/Y controller, giving you the ability to control 3 things at once assuming you don't want one hand free to play notes (which I often do).
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