The guitar's tuning is in perfect fourths right up until the B string, creating a major third. Until that shows up, any phrase or passage can easily move from string to string but then requires a slight position shift when you get to the third, then it resumes the standard movement. For guitarists who have been playing that way for years and years, this isn't a big deal. But when you're used to every string being in fourths (or fifths), and have every lick, chord and scale in the same sort of pattern, it can be a real pain!
While I was preparing to sell off old gear in my studio, I was debating on whether or not to part with my guitar, then I realized the solution to my problem; re-tune it! I decided to tune the instrument entirely in fourths so I could instantly adapt my jazz chords, licks and ideas onto it without having to basically learn a whole new instrument. Now, all the chords and phrases that I play on bass and piccolo bass (when in fourths at least; I often use CACG, CACF, and some other really bizarre tunings depending on the song) are exactly the same on guitar.
There are many advantages to playing in this kind of tuning. The first are that your scales, arpeggios, and licks are the same everywhere on the neck when it comes to the finger patterns; you just have to pick a note to start from and go. Chord shapes also move much easier; moving up or down the strings with the same shape just produces the same kind of chord, but a fourth higher or lower. This makes learning how to accompany a song much easier since you no longer have as many shapes to memorize.
The biggest disadvantages are the lack of the traditional open string chords and bar chords. There are some bar chords but you'll only be playing over four or five strings rather than all six and the shapes are a little quirky at first. Playing classical music also requires some acrobatics in the fretting hand since all the notes on the B and E strings have moved down a fret. For me this isn't an issue; I've written arrangements of classical guitar pieces for solo bass (using only five strings at the time on top of it) and have gotten used to really stretching my left hand, and that's on a longer neck as well. Doing that on the shorter guitar neck is much more comfortable.
This is what works best for me when coming from over a decade of bass playing. When playing other stringed instruments, like mandolin, I've never had much trouble knowing where to go or how to make chords since the uniformed tuning makes it so easy to move from one idea to another without having to constantly or radically change shapes or patterns. I've been playing my guitar much more often now that I've switched to all fourths, and I'm hoping to continue to branch out into it for my own compositions and improvisations.