I usually do a 2" difference, and frankly, I don't really like it. My next cake will be a 10" & 6". Check out this pic as an idea (there are more from thus member, too)
http://cakecentral.com//gallery/1934658
I think it will look fine if you are using larger borders on the edges. I typically do a 2" difference but there are times I wish I would have a 4" to accomidate borders.
The most recent cake in my pic is that size.
Annie
I've been making 6", 9' and 12" but find there just isn't enough "ledge" for decorations. besides, the cake tend to look like monoliths. just got a new set of cake dummies and in playing around with them, decided that I like the 4" difference between tiers so much better. my next big wedding cake will be 6", 10" and 14"...I have a smaller wedding cake due next month and i love the proportions of 6"and 10".
I love the proportions of a 6" on a 10" cake. Here are a couple of examples of how it looks:
http://cakecentral.com/gallery/2003044
The bottom two tiers on this are 10/6...not the cupcake tier.
http://cakecentral.com/gallery/2068977
I go by the number of servings they need/are willing to pay for.
I've had people who don't care about the overall picture-- they only want X servings and no way will they agree to extra cake.
Very few bite on "well, this will look better".
And I don't give away servings to sooth my artistic side 
Rae
Food for thought: I have come to prefer a 3 inch difference in the tiers. This is an 8" with a 4" on top. I have since switched to 8" and 5" and I like the proportions better. I guess it a matter of preference.
8" 4"
http://cakecentral.com/gallery/2068465
8" 5"
http://cakecentral.com/gallery/2123102
Most of my two-tiered cakes are now 6 and 10 inches because my batter makes up one of each. I love the size difference. The couple of times I did a smaller difference, I didn't like the way it turned out as much. The shelf difference is definitely better for decorating.
Food for thought: I have come to prefer a 3 inch difference in the tiers. This is an 8" with a 4" on top. I have since switched to 8" and 5" and I like the proportions better. I guess it a matter of preference.
8" 4"
http://cakecentral.com/gallery/2068465
8" 5"
http://cakecentral.com/gallery/2123102
After comparing the pictures for top tiers smaller than 6", I agree. I think it may have something to do with the smaller tiers being not much wider than they are as high...considering that most tiers are at least 4 inches tall.
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