I have been trying to config my keyboard and mouse for a long time so I can comfortably play the Descent series. Doues anyone have a prefered button setup that they can let me in on. I would be super greatful!

If you're using a source port (and you should be - they're much better than the original DOS engine), check the documentation or forums for that port for more suggestions.

For DXX-Rebirth, I like a binding that lets me keep one hand on the mouse and reach all the other frequently used buttons with my other hand. That means you need forward/back, slide left/right, slide up/down, bank left/right, flare, afterburner, and automap near one another. Firing weapons can be done from the mouse buttons (and, if your mouse has enough buttons, some of the other controls can be done from there too). Weapon select keys are slightly less important to me, but if you are the type to change weapons frequently in combat, you may want to get those closer in. Exactly which keys to bind depends on which hand you use to control your mouse. For right-handed mouse use (assuming qwerty keyboard), I use:

Tab - open automap, LeftAlt - slide on (causes keys that would normally turn the ship to slide instead)
Q - bank left, W - forward, E - bank right, R - rear view, T - transfer energy (D2 converter), Y - cruise faster, U - cruise slower
A - slide left, S - backward, D - slide right, F - fire flare, G - afterburner, H - headlight
Z - unused, X - slide down, C - slide up, V - unused, B - drop proximity bomb/smart bomb

Some of these bindings I picked on my own or inherited from the game's defaults. Some are based on a ticket on the Rebirth issue tracker where various people proposed their favorite keybindings to be made default for new pilots.

thanks dude! Yeah I had no idea about the source enegine but there seems to be additional controller support and mouse/keyboard customizations. I dig it!