I don't do gigs and I have been using a PC for a number of years now. I was using an old stereo amp with a decent size "2.1 speaker" setup which got loud enough and didn't color the sound too much. I also have bass and an electronic drum kit so I have a mixer I use to switch inputs and attenuate etc. That amp has since died, so I am now using my old Spyder2 amp.
I put together a reamper kit box (L2A/Line2Amp) which matches impedance for high-z guitar amp input.
Right off the bat, using a guitar amp means not using any of the cab and amp sims, as they sound pretty awful.
I have been using wah, compressor, gain, and fuzz sims and the main problem with all of them is that you need to be especially careful about the gain or volume. Virtually none of them have db meters or any kind of guidance regarding reference levels, and the software often has input and output gain knobs, preset knobs, knobs on the ADC (analog-digital converter "soundcard"), knobs on the PC volume.
So you need to do a lot of work taming the signal path.
If your sim software has any sort of metering (like built into a compressor sim), try using that to visualize the signal. I also found it helpful to toggle pass-through mode to ensure the guitar amp is receiving something very close to what it would see without the PC in the middle.
I don't play around too much with different pedals and sounds so I am actually pretty happy with the result, but I think that the distortion and fuzz tends to be kind of thin and cold sounding compared to real pedals. The basic overdrive and compression kick along with the real amp overdrive is not bad.
One other thing: this stuff is fragile and may not travel well without headaches or excessive fiddling on site.