Depending on the titles, you'll make your money on the Silver Age comics

Also note that in any series, they were sometimes character lineup changes and these can also be worth a good deal. A good example would be Avengers #4, where Captain America was reintroduced. There was also a Spider-man in the upper 90's, I think #96 that has value because it was the first comic published without the comics code approval..
Here are some of the titles that have held value over the years.
DC - Batman believe it or not, some of the newer ones in this series can have value from the Dark Knight
Marvel- X-Men, Spider-man, Fantastic Four, The Hulk, Iron Man
Independent Comics - Small market and it's a hit, or miss
I could kick myself today, I had the whole run of X-Men comics from #1-100, but never cared for the book, so I sold them off many, many, many, years ago. I did hold on to all the Spider-Man comics, which at one time printed up to 4 tittles and that is well over 1,000 comics right there, and several copies of key issues.
The comics to avoid are any mini-series, or one shots, they will never be worth much in our lifetime.
The only one shot I have that is worth something is Iron Man / Sub Mariner #1 and I have 3 issues of that one.
The saddest part is that in today's economy, there is little money for frivolous spending on comics and it is hurting the prices... So if yo can, I would suggest holding them a bit longer.