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I guess I'll bite on this one.
It's totally doable, if you're savvy, to go all ITB with your amp sims and drum samples etc...
The style of music is what's going to determine how believable the end result is.
Some pop rock music will work but other more organic sounding music will not sound right.
I don't work this way for "real" projects but for at home demos and such, I have DKFH superior and Guitar rig 3. It gets the job done well enough, but it's always kinda like looking at a picture rather than a motion picture.
I will use samples and amp sims in the studio for certain things but it's always to enhance something that's already there or create something unnatural as an artistic choice.
From a drum standpoint, it's very hard to capture the vibe of a real kit resonating in a real room, captured with real mics from a drum sample set.... even taking a live kit and totally replacing the kick, snare and toms and keeping the OH's/rooms real will sound way more natural than using a TD-20 kit and triggering everything through something like DKFH superior.
For guitars, I always find the sounds to be too direct and they don't have enough depth to the simulations. The "room ambience" always sounds cheesy, to me. One way around this has been to create the best tone I can get, that sounds more like my amplifiers and pump it out of the studio monitors and recapture it with a mic and a pre, a few inches from the speaker. It lets the amp sim step back a little bit and sit better in the mix.
YMMV
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