At $87 for a 200ml cartridge, ink for the 4900 runs about 44¢ per ml. This is less than the 56¢ per ml I pay for 3880 ink. It appears that 4900 ink is about 21% less costly per ml than 3880 ink.
I get excellent color out of my 3880. The 4900 is supposed to have a slightly larger color gamut. If your images are within the color gamut of the 3880, you may not notice a difference.
Yes, I can preload a few 17 by 25 sheets in the 3880 and not worry about feeding by hand.
The 3880 can print on sheets as small as 4" by 6". I believe that the 4900 has a minimum sheet size of 8" by 10".
The 4900 can handle roll paper. The 3880 does not.
I believe that the 4900 has a vacuum mechanism to hold the paper. My understanding is that this is a big help if your paper has a curl to it.
Epson says that the inks for the 3880 are good for 2 years from the date of manufacturer, or 6 months after being installed. I assume there are similar recommendations for the 4900. Many people report that these are conservative recommendations, and the inks last much longer (although you may want to remove the carts and agitate them every few months).
If you don't print very much, the ink carts in the 4900 may be too big, and the ink could go bad from age before you use it up. THis would negate much of the advantage of the cheaper inks.