Perhaps it may have something to with this:
When I did my current PCLOS install, I was using a single monitor (Acer P193W) with the onboard graphics (nVidia nForce 6100-430), which uses the same drivers as the 8500GT. Recently, I installed my 8500GT card, disabled the onboard graphics and hooked up the second monitor (HSP M19W2). Perhaps there's some remnants of the old config kicking about and causing some sort of conflict? I feel yet another re-install coming on

Regards .....
That sounds like a clue scooby-doo! Wondering if you might could re-produce the issue, and post both a copy of the generated xorg.conf file, and also the one generated after you have applied your settings in Nvidia? Might help one of the ninja's de-cipher.
Recently, I installed my 8500GT card, disabled the onboard graphics and hooked up the second monitor (HSP M19W2).
Stupid question here, sorry, but you disabled the onboard graphics in BIOS yes?
Might check in /etc/nvidia-current/nvidia-settings.xinit , here's what my machine says :
# to be sourced
#
# Do not modify this file; the changes will be overwritten.
# If you want to disable automatic configuration loading, create
# /etc/sysconfig/nvidia-settings with this line: LOAD_NVIDIA_SETTINGS="no"
#
LOAD_NVIDIA_SETTINGS="yes"
[ -f /etc/sysconfig/nvidia-settings ] && . /etc/sysconfig/nvidia-settings
[ "$LOAD_NVIDIA_SETTINGS" = "yes" ] && /usr/bin/nvidia-settings --load-config-only
And for reference, here's my xorg.conf, this is on my machine with a 6200tc, same drivers just different card, so should be similar:
# nvidia-settings: X configuration file generated by nvidia-settings
# nvidia-settings: version 256.53 (root@localhost.localdomain) Fri Oct 29 16:32:37 CDT 2010
# File generated by XFdrake (rev )
# **********************************************************************
# Refer to the xorg.conf man page for details about the format of
# this file.
# **********************************************************************
Section "ServerLayout"
Identifier "layout1"
Screen 0 "Screen0" 0 0
InputDevice "Keyboard0" "CoreKeyboard"
InputDevice "Mouse0" "CorePointer"
Option "Xinerama" "0"
EndSection
Section "Module"
Load "dbe" # Double-Buffering Extension
Load "v4l" # Video for Linux
Load "extmod"
Load "glx" # 3D layer
Disable "dri"
EndSection
Section "ServerFlags"
# allows the server to start up even if the mouse does not work
#DontZoom # disable <Ctrl><Alt><KP_+>/<KP_-> (resolution switching)
Option "DontZap" "False" # disable <Ctrl><Alt><BS> (server abort)
Option "allowmouseopenfail"
EndSection
Section "InputDevice"
# generated from data in "/etc/sysconfig/keyboard"
Identifier "Keyboard0"
Driver "kbd"
Option "XkbLayout" "us"
Option "XkbModel" "pc105"
EndSection
Section "InputDevice"
# generated from default
Identifier "Mouse0"
Driver "mouse"
Option "Protocol" "auto"
Option "Device" "/dev/psaux"
Option "Emulate3Buttons" "no"
Option "ZAxisMapping" "4 5"
EndSection
Section "Monitor"
# TV fullscreen mode or DVD fullscreen output.
# 768x576 @ 79 Hz, 50 kHz hsync
Identifier "monitor1"
VendorName "Plug'n Play"
ModelName "DELL 2001FP"
HorizSync 31.0 - 80.0
VertRefresh 56.0 - 76.0
ModeLine "768x576" 50.00 768 832 846 1000 576 590 595 630
ModeLine "768x576" 63.07 768 800 960 1024 576 578 590 616
EndSection
Section "Monitor"
Identifier "Monitor0"
VendorName "Unknown"
ModelName "ViewSonic A110"
HorizSync 30.0 - 97.0
VertRefresh 50.0 - 180.0
EndSection
Section "Device"
Identifier "device1"
Driver "nvidia"
VendorName "nVidia Corporation"
BoardName "NVIDIA GeForce 6100 and later"
Option "DPMS"
Option "TwinViewOrientation" "Clone"
Option "TwinView"
Option "AddARGBGLXVisuals"
EndSection
Section "Device"
Identifier "Device0"
Driver "nvidia"
VendorName "NVIDIA Corporation"
BoardName "GeForce 6200 TurboCache(TM)"
EndSection
Section "Screen"
Identifier "screen1"
Device "device1"
Monitor "monitor1"
DefaultDepth 24
SubSection "Display"
Depth 8
Modes "1600x1200" "1400x1050" "1280x1024" "1280x960" "1152x864" "1024x768" "832x624" "800x600" "640x480" "480x360" "320x240"
EndSubSection
SubSection "Display"
Depth 15
Modes "1600x1200" "1400x1050" "1280x1024" "1280x960" "1152x864" "1024x768" "832x624" "800x600" "640x480" "480x360" "320x240"
EndSubSection
SubSection "Display"
Depth 16
Modes "1600x1200" "1400x1050" "1280x1024" "1280x960" "1152x864" "1024x768" "832x624" "800x600" "640x480" "480x360" "320x240"
EndSubSection
SubSection "Display"
Depth 24
Modes "1600x1200" "1400x1050" "1280x1024" "1280x960" "1152x864" "1024x768" "832x624" "800x600" "640x480" "480x360" "320x240"
EndSubSection
EndSection
Section "Screen"
Identifier "Screen0"
Device "Device0"
Monitor "Monitor0"
DefaultDepth 24
Option "TwinView" "1"
Option "TwinViewXineramaInfoOrder" "DFP-0"
Option "metamodes" "CRT: 1280x1024 +1280+0, DFP: 1280x1024 +0+0; CRT: 1280x960 +1280+0, DFP: 1280x960 +0+0; CRT: 1152x864 +1152+0, DFP: 1152x864 +0+0; CRT: 1024x768 +1024+0, DFP: 1024x768 +0+0; CRT: 832x624 +832+0, DFP: 832x624 +0+0; CRT: 800x600 +800+0, DFP: 800x600 +0+0; CRT: 640x480 +640+0, DFP: 640x480 +0+0; CRT: 320x240 +320+0, DFP: 320x240 +0+0"
SubSection "Display"
Depth 24
EndSubSection
EndSection