Safeguards are known:
- Instrument rated pilots
- special, expensive, instruments (radars, etc...)
- extra pair of skilled eyes (2 pilots)
- n + 1 engines / APU
- bigger planes that have less restrictions (more power which means you can bring more weight (more luggage), take off safely from higher altitude, manoeuvre in higher cross winds etc....)
Those companies that fly those airplanes with those pilots already exists, there are known as air taxi and small air charters.