Well, last year I built a “Mega DOS” PC similar to what you have in mind.
The motherboard I use is an EP-7KXA, which is for Slot A CPUs, has one ISA and one AGP slot. After getting around some issues like the 40Gb hard drive causing general protection fault errors in Windows 98 (solved by limiting its size to 32Gb through its jumpers) and instability running 3d accelerated games (reducing RAM from 512 to 256 solved it, maybe patching windows 98 could also work but I didn’t bother), it turned out to be a wonderful all-around DOS machine.
With it I use an Athlon 750mhz CPU, a Geforce 4 MX440 64mb AGP and an ISA Sound Blaster AWE64. All my DOS games work great as the CPU speed can be controlled using THROTTLE (the chipset allows 16 levels of throttling through hardware) and caches can be disabled using SETMUL, which gives me speeds around the 386 DX40. Newer DOS games like Blood, Shadow Warrior, Tomb Raider and Screamer 2 run very smoothly in 640x480 resolution.
Some speed sensitive games I play with it:
-Alone in the Dark (caches disabled, otherwise impossible to get the character to run)
-Alone in the dark 2 (using throttle as disabling cache will be too slow, game runs smooth, with music and the character can run)
-XCOM & XCOM 2(using throttle as it runs too fast in full speed but too slow with caches disabled)
-Warcraft (using throttle to have better scrolling speed)
-Theme Park (using throttle or game runs too fast)
-Ultima 8 (has problems with too much RAM, can be solved by creating a RAM drive to fill some of the RAM)
-Blackthorne (using throttle as there is no music if CPU is too fast)
-Alien Breed (caches disabled for sound and also needs the RAM drive workaround as the copy protection screen gets stuck with more than 32 megs of RAM)
-Descent (using throttle OR running in it in 640x480, the latter one being what I use)
Hope this information helps.
LO-RES, HI-FUN
My DOS/ Win98 PC specs
EP-7KXA Motherboard
Athlon Thunderbird 750mhz
256Mb PC100 RAM
Geforce 4 MX440 64MB AGP (128 bit)
Sound Blaster AWE 64 CT4500 (ISA)
32GB HDD