Based on my experience: Forbid saving in active combat in any way. Think fallout new vegas: can save if hostiles nearby but not if shooting each other.
Save in combat like F2 or Silent Storm make us exploit that tool too much. it's in our nature to use ANY tool we can, and over use BETTER tool than worse ones.
Dont even talk about "self control" or "no abuse moral" like a moron or noob in gaming field! In video games we just use any legal tool within our hands.
+++ Some will use logical reason like you need to save during too-long or too-big fights. While it's quite valid, on paper, it open door to over-abuse save/reload. The answer to that reason is control pacing and terrain from the development stages. Ensure that player should always be able to have a safe place to save after 20 minutes of playing, either by setting safe space, OR just AUTO-SAVE, biatch! set about 10 autosave slots and 15 minutes interval.
+++ Some talk about metagaming, but it's not about that. It's about acknowledging that save/reload is the most powerful tool in the hand of gamers, and developers need to control the degree they can abuse that tool. The difference between manual saving and 10 autosave/15min interval is that the control lie in the hand of developers, not gamers. Without that tool fully in their own hands, they wont build up the bad habit of overuse reloads.
IF it's unavoidably to have a combat-save feature, for whatever reason I dont care to know, then it's necessary to implement something to reward a straight play instead of getting interupted with reloads.
Get a mechanic that recognize a reload into combat zone, and change the loot/regenerated equipments downward compared to standard fare. Say, does it record equipments of combatants? If no, when they reload, make the standard, non-quest, loadouts of the hostiles get reduced in either quality or number, so that player's harvest will be lesser. If it does record, then does it record level or xp reward? If no, then reduce the level or xp reward down a notch.
The reasoning is: since you have to reload during combat, it mean things get too hot for players to handle. In which case we reduce the difficulty for you. No need to thank us~
OR HELL, if the downgrade thing is too hard (more script to calculate) then set a straight-play-bonus/gift after a fight and the reload thing will disable this straight play bonus, everything else the same.