blood 2 tips n tweaks
use alchemy if you have an x-fi. a3d sounds better than eax.
blood2 crashes using HD resolutions. use 1600 or lower.
-it just stretches the screen anyway.
Compatibility modes are probably not necessary. 98 mode was originally needed to get music working, but not after someone hacked AM18.dll. GOG's version seems to already implement a similar tweak.
98 mode will also limit your resolutions.
disabling desktop composition or 3d effects may be necessary for flickering screens.
Vista/7's 3d desktop used to cause problems with blood2, but I haven't noticed it in GOG's version.
-disabling visual themes does the trick, and is enabled by default.
Single pass multitexturing looks terrible, and causes a lot of color banding. Don't use it.
Don't use any of blood2's disable options, especially for graphics.
Lowering Maxfps is a bad idea. Use vsync if you really need to limit fps.
Optimized surfaces can also be disabled to troubleshoot menu/hud problems.
Mipmap sharpening seems to be an outdated ati specific setting, probably better to disable this and enable AF.
The mousewheel can be reversed by editing the autoexec.cfg file.
You can also add 32-bit color here, but I don't know if it actually does anything.
Use F1 in-game to see the weapon list, f5/f6 quicksaves, tab for tips.
You can shoot the pistol faster by clicking.
My favorite level is center for disease management, since it was fairly similar to half-life, but with better graphics.
Foot-soldiers after being shot several times will kamikaze attack. Good for a quick laugh.

Got any tips for the wonky mouse control? No smoothing setting does the trick.

GOG's default setting's seemed to work fairly well, and I decreased the sensitivity, other than that I'm not having any difficulty with the mouse.
I have had mouse problems before with the original blood2, and there are different things you can try.
I think it's primarily an issue with new high-dpi gaming mice, and using lower dpi settings might help. The problem could also be with the mice updating too quickly.
If you're using the microsoft mouse driver, update it to the latest official mouse driver for your mouse, or vice-versa.
Disabling the smoothing or setting it high may help, and also try disabling window's mouse acceleration.
I've have several old games give me problems when using mouse acceleration.
I'm currently using a mx518 with no problems.

Any way to adjust brightness? Some areas are pretty well lit but others are a bit dark for my monitor.

If you can't get the in-game gamma settings to work, even with updated drivers, you'll have to find a way to bypass it.
If your driver supports individual game profiles, you may be able to overwrite gamma here, otherwise, you'll need a 3rd party utility such as ati tray tools, or powerstrip.
ATT and Powerstrip support hot-keys that can change gamma on the fly, and game profiles.
ctrl-alt-num+ increases
ctrl-alt num- decreases
ctrl-alt-f1 resets
hope that helps.
list of programs you can use here:
http://majorgeeks.com/downloads22.html
DarkAdapted is another program you can try.

Trying right now...
Edit: Didnt seem to work for me.
I compiled this script:
#IfWinActive DOSBox
*WheelUp::Send [, {Blind} {z down} sleep 500 {z up}
*WheelDown::Send ], {Blind} {q down} sleep 500 {q up}
Ran the file
changed the options in blood to those keys and it didnt work D:.

No smooting or acceleration in Windows. Tried all the smoothing settings in Blood 2. MX518. Updated to newest driver.
How do I change the dpi?

the plus and minus buttons on the mouse. I'm not having any problems with my mx518, so your problems may be video related.
my sensitivity is "1.790000", and input is set a notch past smooth.

Seems to just change the sensitivity. My fps ingame is good, but the mouse will stutter and jerk. Not sure what to try outside of mouse settings.

try vsync and triple buffering.
If you're using an athlon x2, then it could be a cpu-timer issue, and you'd need amd's hotfix for that.

Tried them, didn't fix. Got a saved game when I'm in the water and it's better there. But when I get up it starts stuttering. CPU is an old Athlon64.

Figures. Probably a timer issue.
Games like the original Unreal will also have problems running if this is the problem.
Install this patch:
http://support.amd.com/us/Pages/dynamicDetails.aspx?ListID=c5cd2c08-1432-4756-aafa-4d9dc646342f&ItemID=153&lang=us

"Input string was not in a correct format."
Did you mean http://support.amd.com/us/Pages/dynamicDetails.aspx?ListID=c5cd2c08-1432-4756-aafa-4d9dc646342f&ItemID=153&lang=us
Dual-Core optimizer? Athlon64 is single core.

Yes, I must have messed up the url last time I edited my post.
The athlon 64's timer doesn't work right, dual-core or not, so if you can get this patch installed, it should help.