-Disable all autosaves, get used to saving manually and regularly.
-Save in different slots.
-Do not overwrite, but delete an old save as you make a new one.
-Keep your total number of saves low. About a dozen max.
-Youre going to have to play janitor for a bit, at least until 1.6. Pick every nirnroot as soon as you see it and pick up the weapons enemies drop on death. Nirnroot has a problem with stacking glows and fallen weapons do not despawn, both contribute to save game bloating.
-Every once in a while it may help to wait 31 days in a small interior cell, to allow all other cells to reset.