Both, frame to match your old holes is best. If not, I just use a roof sealant caulk. My favorites are "Tite Bond" and "Solar Seal". Tight bond is more like a rubber. Great for "building" filler for big holes. Can be applied in wet conditions. Also has pretty high temp specs.
Tight Bond is greasier, takes the sun better without cracking over time, and can be molded after application with wet hand. Won't apply in wet conditions.
Either one can be bought in color to match most metal specs.
As far as I know, TiteBond doesn't come in "clear". Only Solar Seal.
Application: depends on how much aesthetics mean to you. I usually just make a small dollop on each hole about the size of a dime or less.
If we are fixing a mistake on a barn to sell or somewhere that we don't want it to be noticed....then we make sure the metal is flat with no slivers. put a big glob on the back side of the metal and let is ooze through to the front, let it set up to stiff (over night usually), and then carefully take a new razor blade and cut it cleanly at the surface of the metal. Then a dab of touch-up paint to "blend" it with the surrounding paint. That takes a lot of time though. So, here at the house, I just live with the looks, try to use old metal where it won't be noticed, or just take satisfaction in knowing that you saved a couple thousand dollars on metal for that project.
We've used a lot of products on roofing. Never found any others that I recommend.
Also, I have no experience with cold weather situations. Our concerns are always heat not cold and freezing. May need to check out these products on that end of the scale too where you are.