I'd just like to post that I had the same issue on my laptop; Windows 8.1. The .reg file in this thread fixed my issue.
I'm using two external monitors via display port, Paint.NET on primary monitor. Native screen resolution is 2560 x 1440. All other applications render fonts correctly, but Paint.NET was really messed up. It's almost like it was subpixel rendering the fonts with incorrect knowledge of the pixel colour components (ie: RGB vs BGR).
Here's a copy of my Diagnostics information:
Application paint.net 4.0.1 (Final 4.1.5306.43142)
Build Date Saturday, 12 July 2014
Hardware accelerated rendering (GPU) True
Animations True
DPI 96.00 (1.00x scale)
Language en-US
OS Windows 8.1 (6.3.9600.0)
.NET Runtime 4.0.30319.34014
Physical Memory 16,323 MB
CPU IntelĀ® Core i7-4900MQ CPU @ 2.80GHz
Architecture x64 (64-bit)
Process Mode 64-bit
Speed ~2794 MHz
Cores / Threads 8
Features DEP, SSE, SSE2, SSE3, SSSE3, SSE4_1, SSE4_2, XSAVE
Video Card NVIDIA Quadro K2100M
Dedicated Video RAM 1,958 MB
Dedicated System RAM 0 MB
Shared System RAM 8,161 MB
Vendor ID 0x10DE
Device ID 0x11FC
Subsystem ID 0x05CC1028
Revision 161
LUID 0x00008839
Flags None
Outputs 2
Video Card Microsoft Basic Render Driver
Dedicated Video RAM 0 MB
Dedicated System RAM 0 MB
Shared System RAM 256 MB
Vendor ID 0x1414
Device ID 0x008C
Subsystem ID 0x00000000
Revision 0
LUID 0x00009309
Flags Software
Outputs 0