These planes are fast
I have made 4 trips from Washington to east coast February to March.
I just take the southern route across AZ and NM. The speed of these planes make it not that much longer. One nice leg I did last Match was Laughlin NV to Albuquerque, flew over the Grand Canyon then up to Monument Valley, dropped down to 1000ish feet AGL for a closer look then landed at Doubke Eagle AEG, for lunch and fuel. Double Eagle is also a nice overnight, great FBO with loaner car, they will get you a good deal on a hotel as well.
It is nice to have an out in case of engine failure, but realize you can really limit yourself route wise. You have to have some faith that the motor will keep running. These engine run for thousands of hours without an issue, it is okay to be in no mans land for 30 minutes of a 4 hour leg. That is my personal opinion, besides you see some beautiful country this way.
Winds in the mountains as said above are the big issue, if you can't clear the range with 1000' per 10 knots of wind don't go. So if wind at altitude of the mountains is 30kts you want to be at least 3000' above or more. Borrow or buy an oxygen system and learn to use it, altitude is your friend. Smoother air, tail winds going east and more time to handle the rare engine out factor.
Even in rough terrain, there are survivable places to land. Speaking of this, I use a fly fishing vest set up with essential survival gear. I also have a sleeping bag and light weight tarp for shelter just in case. I know one guy that vacuum packed his gear in a large plastic storage bag and it is permanently stored in his wingtip, they get inspected every annual. He always has his survival gear with him this way.
More hours in the air is a good thing, don't take a risk just for a lower fuel bill. I will make a longer more comfortable flight every time.
Cheers