Buffers vary in quality. Some sound great, some not so much. A good buffer should allow you to use stage or studio length cables in excess of 30-40 feet with no loss of fidelity. If you use a ten foot cable between the guitar and the buffer, you're better off than if you use a 20 foot cable between the guitar and the buffer. However, after the buffer, you should be able to run some fairly long cable lengths, and certainly more than 4 pedals.
The cables between pedals, guitar, and amp can also affect the tone. The pedals themselves can affect the tone, depending on whether they really are true bypass (there are a few types of bypass labeled true bypass that arguably are not really true bypass). Of course, a pedal like a Boss with a built in low quality buffer circuit imposes its own limitations on the rest of the chain and becomes the weak link.
If you're fussy about tone, you have to think of the pedalboard as a system, and all the stuff on the board as audio components. So using isolated power supplies (such as Voodoo Labs) to prevent noise caused by ground loops and other pedal interactions, is one step. I've found that using one type of good cable for consistency and for resistance to RFI and EMI is another step. Using high quality pedals, whether or not you believe in true bypass, is yet another step. Basically, noise, whether coming from ground loops, or electromagnetic interference, is the enemy of fidelity and detail, because even low levels of noise will mask detail. Not to mention that noise sounds annoying. A good power supply is an important step, or just use batteries.
Most tuners are buffered, and sound terrible, not because buffers are bad, but because the buffers in most pedals are junk. I usually run a tuner either into a true bypass loop or if a buffer has a tuner or aux output, I use that for the tuner.
Currently I'm running a Suhr buffer into four true bypass pedals and a true bypass box looper. So far it's got the best fidelity of several buffers I've tried in terms of keeping the subtle high end detail happening. I've had buffers that were too bright, and buffers that preserved the frequency balance but took some of the life and detail out of the signal.
I run one or two more digital pedals in the looper depending on needs. The main purpose of the looper is to keep the direct path from the guitar into the amp analog. The buffer also has a second output that I use for a tuner.
The Suhr buffer preserves the signal well enough from the pedal board that I can use a 25 foot cable from the pedalboard to the amp, plus the pedal interconnects. That means I have 30 feet of cables and plugs, plus pedals, following the buffer with no signal loss that I can detect. I've switched over to PRS/VanDamme cables for everything between the guitar and the amp. It's pretty neutral sounding, very flexible, is less susceptible to noise than my other good cables, etc., and it just works. Whether I can get the same signal integrity for this kind of length with other cables using the Suhr box is something I haven't tried.
In terms of less than great sound, but sound that is still acceptable, I've found that the buffer on the latest Boss tuner isn't all that bad, if you run it first in the signal chain. It's not as clear as the Suhr, and not as transparent, but for a Boss tuner it's their best yet.