Survival Mode is... poorly balanced. It has several issues.
You get this "Adrenaline" Perk that increases the damage you deal in combat by 5% per rank. You gain a rank by killing 5 targets. You loose ranks by sleeping. Since you MUST sleep (or your character suffers increasingly terrible debuffs) this sort of comes out being a wash.
Fatigue is a new mechanic that is similar to Radiation damage, except that it reduces your maximum Action Points. Fatigue increases by not sleeping, eating or drinking. If you don't use VATS, Fatigue does not seem to be a big deal.
You have a Wellness stat now. If your Wellness is low, you'll get "sick" (random debuffs). Your Wellness goes up by sleeping, eating and drinking often. It goes down by using chems, taking a MASSIVE hit every time you use Rad-away (I get some illness after using 3 Rad-aways). Sickness is nearly identical to being Addicted. Visit a doctor or take an Antibiotic and it goes away. However, if your Wellness is still low, you'll just get sick again in a few minutes. I understand that they wanted to add some penalty for relying on chems (especially Rad-away), but this just seems tedious.
Food and water are not a huge problem. Getting "restful sleep" is. You can't sleep as long on a blood stained mattress as you can in a down filled bed. This often leads to taking "cat naps" at every opportunity.
Companions that are "knocked out" of a fight won't die. They leave you, and return "home". You do have a short window to heal them before they get fed up and leave, but I have had a couple of instances where the fight ran long and they left before I could heal them. With fast travel disabled, this became annoying fairly quickly.
Removing fast travel makes the Minutemen faction incredibly tedious. I avoid Preston or unlocking the Castle to reduce the amount of walking involved in saving every sorry sod in the Commonwealth.
The decision to reduce maximum carry load coupled with no fast travel makes looting for settlement expansion a chore. Since everything now has weight, you must carry the essentials to survive (water, food, clothing, weapons, healing items, etc) so there is less room for typewriters and duct tape. The respawn timers of "cleared" areas is doubled, so you can make 10 actual trips back and forth looting large locations without fear that things will respawn.
I've found that Survival Mode makes low level gameplay punitive and mid to high level gameplay tedious.