Hypothetically, yes...though if your board has a configuration of x16/x1/x16/x1 on your 4 PCIe slots, then you can just make sure you install your cards into the x16 slots and leave the x1 slots open. Most MBs have different configurations for the PCIe slots to accommodate different needs.
To be certain of possible configurations, I would go to www.asus.com and check the MB you chose (by model number) and verify the configuration available on the PCIe slots for the board.
If the configuration is something like x8/x4/x8/x4 then you won't get full performance out of the GTX 780s (though the difference between x16 and x1 is a great deal, the difference between x8 and x16 is considerably less). You would only really run into situations where your frame rate dips in apps/games that use a tremendous amount of bandwidth. Right now that isn't many, but in the future it may be more.
Additionally, if the difference is between both at x16 or both at x8 your drop in frame rates would likely be somewhere in the neighborhood of 6-8% performance loss between the 2 cards. So you're not talking a huge amount...6-8 FPS @ 100 FPS average. You should still see playable frames without issue.
I would check the manufacturers listing of configurations first though, and there may be other boards with a more favorable x16/x1/x16/x1 configuration...(I know Asus has some for socket 1155/1150/AM3+ but you might have to go to something like a sabertooth to get it).