Actually, if you restrict yourself to a hypothetical "need to build something Shuttle like using available technology" universe then you can get something safer fairly easily. Buran, for example, was considerably safer for a few reasons, but we could make something even safer.
First, ditch the SRBs, they are a severe safety hazard (they led to one Shuttle disaster, for example) because they are segmented, they can't be throttled, they can't be turned off, etc. That leaves you with a thrust problem though, due to the low thrust of LOX/LH2 engines. So, second, replace LOX/LH2 with LOX/Kerosene. Now you have plenty of thrust, now you don't have to deal with super-cryogenic fluids, now you don't have to eke out every possible mass ratio boost on the ET because both LOX and Kerosene are fairly dense. Now you can ditch the foam insulation, and ice formation is slightly less of a problem.
Third, take the engines off the orbiter and put them on the booster (ET). Now you've created a vehicle, like Energia, which you can launch non-Orbiter cargo with. Realistically you haven't made things more expensive by throwing away expensive high performance engines every trip because it takes so long to inspect, refurbish, and re-install the SSMEs on the orbiter anyway that it's a wash money-wise, and probably for the best time-wise. On the plus side now the orbiter doesn't have to support the thrust of giant engines so its frame can be made lighter. Also, it doesn't have to bring those engines back down to Earth, so it can be yet lighter again.
Fourth, snip the wings off the orbiter. Turns out the military didn't really need a several hundred mile cross-range landing flight capability on the orbiter because the super-hypothetical mission that was designed for never turned out to be even remotely practical. So, smaller wings mean less mass and, again, a lighter frame. Now you've reduced the orbiter mass by a crap-ton and gotten rid of the huge amount of super vulnerable leading-edges on the wings. Now you can use a less sophisticated thermal shielding system on the orbiter (since it's lighter, smaller, and barely has wings at all), you don't need the carbon-carbon composite wing leading-edge bits, you don't need the vulnerable ceramic tiles that need to be meticulously inspected after every flight.
Now you have a vehicle that is much simpler and safer and yet does essentially everything that the old Shuttle system actually did in practice.
Granted, if you were designing something from a clean sheet at this point you would never end up with anything even remotely resembling the Shuttle.
First, ditch the SRBs, they are a severe safety hazard (they led to one Shuttle disaster, for example) because they are segmented, they can't be throttled, they can't be turned off, etc. That leaves you with a thrust problem though, due to the low thrust of LOX/LH2 engines. So, second, replace LOX/LH2 with LOX/Kerosene. Now you have plenty of thrust, now you don't have to deal with super-cryogenic fluids, now you don't have to eke out every possible mass ratio boost on the ET because both LOX and Kerosene are fairly dense. Now you can ditch the foam insulation, and ice formation is slightly less of a problem.
Third, take the engines off the orbiter and put them on the booster (ET). Now you've created a vehicle, like Energia, which you can launch non-Orbiter cargo with. Realistically you haven't made things more expensive by throwing away expensive high performance engines every trip because it takes so long to inspect, refurbish, and re-install the SSMEs on the orbiter anyway that it's a wash money-wise, and probably for the best time-wise. On the plus side now the orbiter doesn't have to support the thrust of giant engines so its frame can be made lighter. Also, it doesn't have to bring those engines back down to Earth, so it can be yet lighter again.
Fourth, snip the wings off the orbiter. Turns out the military didn't really need a several hundred mile cross-range landing flight capability on the orbiter because the super-hypothetical mission that was designed for never turned out to be even remotely practical. So, smaller wings mean less mass and, again, a lighter frame. Now you've reduced the orbiter mass by a crap-ton and gotten rid of the huge amount of super vulnerable leading-edges on the wings. Now you can use a less sophisticated thermal shielding system on the orbiter (since it's lighter, smaller, and barely has wings at all), you don't need the carbon-carbon composite wing leading-edge bits, you don't need the vulnerable ceramic tiles that need to be meticulously inspected after every flight.
Now you have a vehicle that is much simpler and safer and yet does essentially everything that the old Shuttle system actually did in practice.
Granted, if you were designing something from a clean sheet at this point you would never end up with anything even remotely resembling the Shuttle.