Balanced vs Maximized Codon Optimization
Codon usage optimization is still pretty much heurestic. The most common factor we think are important in E. Coli are:


optimization to highly expressed genes, i.e. maximization of codon adaptation index http://www.ncbi.nlm.nih.gov/pubmed/19359587/
keeping the optimal GC content http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0107319
not introducing motifs that are somehow detrimental, e.g. restriction enzymes, or some dinucleotides http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0056642
adapting to available tRNA http://www.plosone.org/article/info:doi/10.1371/journal.pone.0007002
minimizing folding energy (in the first ca. 30 codons) and minimizing the amount of hairpins at the 5' end http://www.sciencedirect.com/science/article/pii/S0014579305010719
optimization of 'codon context' e.g. dicodons but also using nonoptimal codons between secondary structure for more accurate folding http://www.ncbi.nlm.nih.gov/pubmed/15772378
optimization of codon balance and also maybe the introduction of a 'ramp of slow codons' in the beginning of a gene to avoid 'traffic jams' of ribosomes later on. http://www.ncbi.nlm.nih.gov/pubmed/20403329


Most probably it's a mixture of all of those.

Disclaimer: We are working on a codon optimization strategy for e.coli/yeast/hela and it works in e. coli but is yet untested in human cells. If you want to take a long shot just shoot me a message and we could try it. Apart from this, I would also offer you to have a look at your sequence and see if there is anything 'strange' from the codon usage point of view and what I think what be the best optimization strategy.